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  • 301.
    Ohlsson, Tommy
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Particle Physics.
    Another collider is not the way forward2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 494, no 7435, 35-35 p.Article in journal (Other academic)
  • 302.
    Ohlsson, Tommy
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Particle Physics.
    Don't let furore over neutrinos blur results2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 485, no 7398, 309-309 p.Article in journal (Refereed)
  • 303.
    Ohlsson, Tommy
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Particle Physics.
    International Linear Collider: Another collider is not the way forward2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 494, no 7435Article in journal (Refereed)
  • 304.
    Ohlsson, Tommy
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Particle Physics.
    Preprint servers: Follow arXiv's lead2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 489, no 7416, 367- p.Article in journal (Refereed)
  • 305. Okada, Yukinori
    et al.
    Wu, Di
    Trynka, Gosia
    Raj, Towfique
    Terao, Chikashi
    Ikari, Katsunori
    Kochi, Yuta
    Ohmura, Koichiro
    Suzuki, Akari
    Yoshida, Shinji
    Graham, Robert R
    Manoharan, Arun
    Ortmann, Ward
    Bhangale, Tushar
    Denny, Joshua C
    Carroll, Robert J
    Eyler, Anne E
    Greenberg, Jeffrey D
    Kremer, Joel M
    Pappas, Dimitrios A
    Jiang, Lei
    Yin, Jian
    Ye, Lingying
    Su, Ding-Feng
    Yang, Jian
    Xie, Gang
    Keystone, Ed
    Westra, Harm-Jan
    Esko, Tonu
    Metspalu, Andres
    Zhou, Xuezhong
    Gupta, Namrata
    Mirel, Daniel
    Stahl, Eli A
    Diogo, Dorothee
    Cui, Jing
    Liao, Katherine
    Guo, Michael H
    Myouzen, Keiko
    Kawaguchi, Takahisa
    Coenen, Marieke JH
    van Riel, Piet LCM
    van de laar, Mart AFJ
    Guchelaar, Henk-Jan
    Huizinga, Tom WJ
    Dieude, Philippe
    Mariette, Xavier
    Bridges, S Louis, Jr.
    Zhernakova, Alexandra
    Toes, Rene EM
    Tak, Paul P
    Miceli-Richard, Corinne
    Bang, So-Young
    Lee, Hye-Soon
    Martin, Javier
    Gonzalez-Gay, Miguel A
    Rodriguez-Rodriguez, Luis
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Ärlestig, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Choi, Hyon K
    Kamatani, Yoichiro
    Galan, Pilar
    Lathrop, Mark
    Eyre, Steve
    Bowes, John
    Barton, Anne
    de Vries, Niek
    Moreland, Larry W
    Criswell, Lindsey A
    Karlson, Elizabeth W
    Taniguchi, Atsuo
    Yamada, Ryo
    Kubo, Michiaki
    Liu, Jun S
    Bae, Sang-Cheol
    Worthington, Jane
    Padyukov, Leonid
    Klareskog, Lars
    Gregersen, Peter K
    Raychaudhuri, Soumya
    Stranger, Barbara E
    De Jager, Philip L
    Franke, Lude
    Visscher, Peter M
    Brown, Matthew A
    Yamanaka, Hisashi
    Mimori, Tsuneyo
    Takahashi, Atsushi
    Xu, Huji
    Behrens, Timothy W
    Siminovitch, Katherine A
    Momohara, Shigeki
    Matsuda, Fumihiko
    Yamamoto, Kazuhiko
    Plenge, Robert M
    Genetics of rheumatoid arthritis contributes to biology and drug discovery2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 506, no 7488, 376-381 p.Article in journal (Refereed)
    Abstract [en]

    A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

  • 306.
    Okbay, Aysu
    et al.
    Erasmus Univ, Erasmus Sch Econ, Dept Appl Econ, NL-3062 PA Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, NL-3062 PA Rotterdam, Netherlands..
    Beauchamp, Jonathan P.
    Harvard Univ, Dept Econ, Cambridge, MA 02138 USA..
    Fontana, Mark Alan
    Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA 90089 USA..
    Lee, James J.
    Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN 55455 USA..
    Pers, Tune H.
    Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, DK-2100 Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark..
    Rietveld, Cornelius A.
    Erasmus Univ, Erasmus Sch Econ, Dept Appl Econ, NL-3062 PA Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, NL-3062 PA Rotterdam, Netherlands..
    Turley, Patrick
    Harvard Univ, Dept Econ, Cambridge, MA 02138 USA..
    Chen, Guo-Bo
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia..
    Emilsson, Valur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Pharmaceut Sci, IS-107 Reykjavik, Iceland..
    Meddens, S. Fleur W.
    Erasmus Univ, Inst Behav & Biol, NL-3062 PA Rotterdam, Netherlands.;Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands.;Univ Amsterdam, Amsterdam Business Sch, NL-1018 TV Amsterdam, Netherlands..
    Oskarsson, Sven
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Government.
    Pickrell, Joseph K.
    New York Genome Ctr, New York, NY 10013 USA..
    Thom, Kevin
    NYU, Dept Econ, New York, NY 10003 USA..
    Timshel, Pascal
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark..
    de Vlaming, Ronald
    Erasmus Univ, Erasmus Sch Econ, Dept Appl Econ, NL-3062 PA Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, NL-3062 PA Rotterdam, Netherlands..
    Abdellaoui, Abdel
    Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands..
    Ahluwalia, Tarunveer S.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, DK-2820 Copenhagen, Denmark.;Steno Diabet Ctr, DK-2820 Gentofte, Denmark..
    Bacelis, Jonas
    Sahlgrens Acad, Inst Clin Sci, Dept Obstet & Gynecol, S-41685 Gothenburg, Sweden..
    Baumbach, Clemens
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany..
    Bjornsdottir, Gyda
    Brandsma, Johannes H.
    Erasmus MC, Dept Cell Biol, NL-3015 CN Rotterdam, Netherlands..
    Concas, Maria Pina
    Natl Res Council Italy, UOS Sassari, Ist Ric Genet & Biomed, I-07100 Sassari, Italy..
    Derringer, Jaime
    Univ Illinois, Psychol, Champaign, IL 61820 USA..
    Furlotte, Nicholas A.
    23andMe Inc, Mountain View, CA 94041 USA..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6500 HB Nijmegen, Netherlands..
    Girotto, Giorgia
    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy..
    Gupta, Richa
    Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland..
    Hall, Leanne M.
    Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Gen Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Hofer, Edith
    Gen Hosp, Dept Neurol, A-8036 Graz, Austria.;Med Univ Graz, A-8036 Graz, Austria.;Gen Hosp, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria..
    Horikoshi, Momoko
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Huffman, Jennifer E.
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Kaasik, Kadri
    Univ Helsinki, Inst Behav Sci, FIN-00014 Helsinki, Finland..
    Kalafati, Ioanna P.
    Harokopio Univ, Nutr & Dietet, Hlth Sci & Educ, Athens 17671, Greece..
    Karlsson, Robert
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Kong, Augustine
    Lahti, Jari
    Univ Helsinki, Inst Behav Sci, FIN-00014 Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki 00014, Finland..
    van der Lee, Sven J.
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    de Leeuw, Christiaan
    Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands.;Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 EC Nijmegen, Netherlands..
    Lind, Penelope A.
    QIMR Berghofer Med Res Inst, Quantitat Genet, Brisbane, Qld 4029, Australia..
    Lindgren, Karl-Oskar
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Government.
    Liu, Tian
    Max Planck Inst Human Dev, Lifespan Psychol, D-14195 Berlin, Germany..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.;Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London SE1 7EH, England..
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Miller, Michael B.
    Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN 55455 USA..
    van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands..
    Oldmeadow, Christopher
    Hunter Med Res Inst, Publ Hlth Stream, New Lambton, NSW 2305, Australia.;Univ Newcastle, Fac Hlth & Med, Newcastle, NSW 2300, Australia..
    Payton, Antony
    Univ Manchester, Inst Populat Hlth, Ctr Integrated Genom Med Res, Manchester M13 9PT, Lancs, England.;Univ Manchester, Sch Psychol Sci, Human Commun & Deafness, Manchester M13 9PL, Lancs, England..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.;THL Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland..
    Peyrot, Wouter J.
    Vrije Univ Amsterdam, Med Ctr, Psychiat, NL-1081 HL Amsterdam, Netherlands.;GGZ inGeest, NL-1081 HL Amsterdam, Netherlands..
    Qian, Yong
    NIA, Genet Lab, Baltimore, MD 21224 USA..
    Raitakari, Olli
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20521, Finland..
    Rueedi, Rico
    Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Salvi, Erika
    Univ Milan, Dept Hlth Sci, I-20142 Milan, Italy..
    Schmidt, Brge
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, D-45147 Essen, Germany..
    Schraut, Katharina E.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Shi, Jianxin
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Smith, Albert V.
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Poot, Raymond A.
    Erasmus MC, Dept Cell Biol, NL-3015 CN Rotterdam, Netherlands..
    St Pourcain, Beate
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.;Univ Bristol, Sch Oral & Dent Sci, Bristol BS1 2LY, Avon, England..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Thorleifsson, Gudmar
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands..
    Vuckovic, Dragana
    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy..
    Wellmann, Juergen
    Univ Munster, Inst Epidemiol & Social Med, D-48149 Munster, Germany..
    Westra, Harm-Jan
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol,Dept Med, Boston, MA 02115 USA.;Partners Ctr Personalized Genet Med, Boston, MA 02115 USA..
    Yang, Jingyun
    Rush Univ, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA..
    Zhao, Wei
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Zhu, Zhihong
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia..
    Alizadeh, Behrooz Z.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, NL-9713 GZ Groningen, Netherlands..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Bakshi, Andrew
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia..
    Baumeister, Sebastian E.
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany.;Univ Regensburg, Inst Epidemiol & Prevent Med, D-93053 Regensburg, Germany..
    Biino, Ginevra
    Natl Res Council Italy, Inst Mol Genet, I-27100 Pavia, Italy..
    Bonnelykke, Klaus
    Univ Bristol, Sch Oral & Dent Sci, Bristol BS1 2LY, Avon, England..
    Boyle, Patricia A.
    Rush Univ, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA..
    Campbell, Harry
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Cappuccio, Francesco P.
    Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    De Neve, Jan-Emmanuel
    Univ Oxford, Said Business Sch, Oxford OX1 1HP, England..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia..
    Demuth, Ilja
    Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13347 Berlin, Germany.;Charite, Inst Med & Human Genet, D-13353 Berlin, Germany..
    Ding, Jun
    NIA, Genet Lab, Baltimore, MD 21224 USA..
    Eibich, Peter
    DIW Berlin, German Socioecon Panel Study, D-10117 Berlin, Germany.;Univ Oxford, Nuffield Dept Populat Hlth, Hlth Econ Res Ctr, Oxford OX3 7LF, England..
    Eisele, Lewin
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, D-45147 Essen, Germany..
    Eklund, Niina
    THL Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland..
    Evans, David M.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.;Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4102, Australia..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48109 USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63018 USA..
    Forstner, Andreas J.
    Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany..
    Gandin, Ilaria
    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy..
    Gunnarsson, Bjarni
    Halldorsson, Bjarni V.
    Reykjavik Univ, Sch Sci & Engn, Inst Biomed & Neural Engn, IS-101 Reykjavik, Iceland..
    Harris, Tamara B.
    NIA, Lab Epidemiol, Demog, NIH, Bethesda, MD 20892 USA..
    Heath, Andrew C.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Hocking, Lynne J.
    Univ Aberdeen, Div Appl Hlth Sci, Aberdeen AB25 2ZD, Scotland..
    Holliday, Elizabeth G.
    Hunter Med Res Inst, Publ Hlth Stream, New Lambton, NSW 2305, Australia.;Univ Newcastle, Fac Hlth & Med, Newcastle, NSW 2300, Australia..
    Homuth, Georg
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17475 Greifswald, Germany..
    Horan, Michael A.
    Univ Manchester, Manchester Med Sch, Manchester M13 9PT, Lancs, England..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands..
    de Jager, Philip L.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, 75 Francis St, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Psychiat, Program Translat NeuroPsychiat Genom, 75 Francis St, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA 02115 USA..
    Joshi, Peter K.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Jugessur, Astanand
    Norwegian Inst Publ Hlth, Dept Genes & Environm, N-0403 Oslo, Norway..
    Kaakinen, Marika A.
    Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London W12 0NN, England..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland..
    Kanoni, Stavroula
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England..
    Keltigangas-Jarvinen, Liisa
    Univ Helsinki, Inst Behav Sci, FIN-00014 Helsinki, Finland..
    Kiemeney, Lambertus A. L. M.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6500 HB Nijmegen, Netherlands..
    Kolcic, Ivana
    Univ Split, Sch Med, Publ Hlth, Split 21000, Croatia..
    Koskinen, Seppo
    THL Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland..
    Kraja, Aldi T.
    Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63018 USA..
    Kroh, Martin
    DIW Berlin, German Socioecon Panel Study, D-10117 Berlin, Germany..
    Kutalik, Zoltan
    Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Lausanne Univ Hosp CHUV, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland..
    Latvala, Antti
    Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland..
    Launer, Lenore J.
    NIA, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA..
    Lebreton, Mael P.
    Univ Amsterdam, Amsterdam Business Sch, NL-1018 TV Amsterdam, Netherlands.;Univ Amsterdam, Amsterdam Brain & Cognit Ctr, NL-1018 XA Amsterdam, Netherlands..
    Levinson, Douglas F.
    Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA..
    Lichtenstein, Paul
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Lichtner, Peter
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Loukola, Anu
    Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland..
    Madden, Pamela A.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Maki-Opas, Tomi
    THL Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland..
    Marioni, Riccardo E.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland..
    Marques-Vidal, Pedro
    Lausanne Univ Hosp CHUV, Dept Internal Med, Internal Med, CH-1011 Lausanne, Switzerland..
    Meddens, Gerardus A.
    Tema BV, NL-2131 HE Hoofddorp, Netherlands..
    McMahon, George
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Meisinger, Christa
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany..
    Meitinger, Thomas
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany..
    Milaneschi, Yusplitri
    Vrije Univ Amsterdam, Med Ctr, Psychiat, NL-1081 HL Amsterdam, Netherlands.;GGZ inGeest, NL-1081 HL Amsterdam, Netherlands..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Montgomery, Grant W.
    QIMR Berghofer Med Res Inst, Mol Epidemiol, Brisbane, Qld 4029, Australia..
    Myhre, Ronny
    Norwegian Inst Publ Hlth, Dept Genes & Environm, N-0403 Oslo, Norway..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Gen Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Nyholt, Dale R.
    QIMR Berghofer Med Res Inst, Mol Epidemiol, Brisbane, Qld 4029, Australia.;Queensland Inst Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4059, Australia..
    Ollier, William E. R.
    Univ Manchester, Inst Populat Hlth, Ctr Integrated Genom Med Res, Manchester M13 9PT, Lancs, England..
    Palotie, Aarno
    Erasmus Univ, Inst Behav & Biol, NL-3062 PA Rotterdam, Netherlands.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA..
    Paternoster, Lavinia
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Petrovic, Katja E.
    Gen Hosp, Dept Neurol, A-8036 Graz, Austria.;Med Univ Graz, A-8036 Graz, Austria..
    Porteous, David J.
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Raikkonen, Katri
    Univ Helsinki, Inst Behav Sci, FIN-00014 Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki 00014, Finland..
    Ring, Susan M.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Robino, Antonietta
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Med Genet, I-34100 Trieste, Italy..
    Rostapshova, Olga
    Harvard Univ, Dept Econ, Cambridge, MA 02138 USA.;Social Impact, Arlington, VA 22201 USA..
    Rudan, Igor
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Rustichini, Aldo
    Univ Minnesota Twin Cities, Dept Econ, Minneapolis, MN 55455 USA..
    Salomaa, Veikko
    THL Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland..
    Sanders, Alan R.
    NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL 60201 USA.;Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA..
    Sarin, Antti-Pekka
    Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland.;Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki 00300, Finland..
    Schmidt, Helena
    Gen Hosp, Dept Neurol, A-8036 Graz, Austria.;Med Univ Graz, A-8036 Graz, Austria.;Gen Hosp, Ctr Mol Med, Inst Mol Biol & Biochem, Res Unit Genet Epidemiol, A-8010 Graz, Austria.;Med Univ, A-8010 Graz, Graz, Austria..
    Scott, Rodney J.
    Univ Newcastle, Fac Hlth & Med, Newcastle, NSW 2300, Australia.;Hunter Med Res Inst, Informat Based Med Stream, New Lambton, NSW 2305, Australia..
    Smith, Blair H.
    Univ Dundee, Res Inst, Dundee DD1 9SY, Scotland..
    Smith, Jennifer A.
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Staessen, Jan A.
    Univ Leuven, Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, B-3000 Leuven, Belgium.;Maastricht Univ, R&D VitaK Grp, NL-6229 EV Maastricht, Netherlands..
    Steinhagen-Thiessen, Elisabeth
    Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13347 Berlin, Germany..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, D-81377 Munich, Germany..
    Terracciano, Antonio
    Florida State Univ, Coll Med, Dept Geriatr, Tallahassee, FL 32306 USA..
    Tobin, Martin D.
    Univ Leicester, Dept Hlth Sci & Genet, Leicester LE1 7RH, Leics, England..
    Ulivi, Sheila
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Med Genet, I-34100 Trieste, Italy..
    Vaccargiu, Simona
    Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA..
    Quaye, Lydia
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    van Rooij, Frank J. A.
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Venturini, Cristina
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.;Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London SE1 7EH, England..
    Vinkhuyzen, Anna A. E.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia..
    Volker, Uwe
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17475 Greifswald, Germany..
    Volzke, Henry
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Vonk, Judith M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands..
    Vozzi, Diego
    Social Impact, Arlington, VA 22201 USA..
    Waage, Johannes
    Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, DK-2820 Copenhagen, Denmark.;Steno Diabet Ctr, DK-2820 Gentofte, Denmark..
    Ware, Erin B.
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.;Univ Michigan, Inst Social Res, Res Ctr Grp Dynam, Ann Arbor, MI 48104 USA..
    Willemsen, Gonneke
    Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands..
    Attia, John R.
    Hunter Med Res Inst, Publ Hlth Stream, New Lambton, NSW 2305, Australia.;Univ Manchester, Inst Populat Hlth, Ctr Integrated Genom Med Res, Manchester M13 9PT, Lancs, England..
    Bennett, David A.
    Rush Univ, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA..
    Berger, Klaus
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands..
    Bertram, Lars
    Univ Lubeck, Inst Neurogenet & Integrat & Expt Genom, Platform Genome Analyt, D-23562 Lubeck, Germany.;Univ London Imperial Coll Sci Technol & Med, Neuroepidemiol & Ageing Res Unit, Sch Publ Hlth, Fac Med, London SW7 2AZ, England..
    Bisgaard, Hans
    Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, DK-2820 Copenhagen, Denmark..
    Boomsma, Dorret I.
    Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63018 USA..
    Bultmann, Ute
    Univ Groningen, Univ Med Ctr Groningen, Dept Hlth Sci Community & Occupat Med, NL-9713 AV Groningen, Netherlands..
    Chabris, Christopher F.
    Union Coll, Dept Psychol, Schenectady, NY 12308 USA..
    Cucca, Francesco
    Cittadella Univ Monserrato, CNR, IRGB, I-9042 Cagliari, Italy..
    Cusi, Daniele
    Univ Milan, Dept Hlth Sci, I-20142 Milan, Italy.;Italian Natl Res Council, Inst Biomed Technol, I-20090 Milan, Italy..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Dedoussis, George V.
    Harokopio Univ, Nutr & Dietet, Hlth Sci & Educ, Athens 17671, Greece..
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Eriksson, Johan G.
    Folkhalsan Res Ctr, Helsinki 00014, Finland.;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FIN-00014 Helsinki, Finland..
    Franke, Barbara
    Donders Ctr Neurosci, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.;Donders Ctr Neurosci, Dept Psychiat, NL-6500 HB Nijmegen, Netherlands..
    Franke, Lude
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands..
    Gasparini, Paolo
    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy.;Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Med Genet, I-34100 Trieste, Italy.;Sidra, Expt Genet Div, Doha 26999, Qatar..
    Gejman, Pablo V.
    NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL 60201 USA.;Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA..
    Gieger, Christian
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany..
    Grabe, Hans-Jorgen
    Univ Med Greifswald, Dept Psychiat & Psychotherapy, D-17475 Greifswald, Germany.;HELIOS Hosp Stralsund, Dept Psychiat & Psychotherapy, D-18437 Stralsund, Germany..
    Gratten, Jacob
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia..
    Groenen, Patrick J. F.
    Erasmus Univ, Erasmus Sch Econ, Econometr Inst, NL-3062 PA Rotterdam, Netherlands..
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, NL-1105 AZ Utrecht, Netherlands..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Generat Scotland, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Hinds, David A.
    23andMe Inc, Mountain View, CA 94041 USA..
    Hoffmann, Wolfgang
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Hyppnen, Elina
    Univ S Australia, Sch Hlth Sci, Ctr Populat Hlth Res, Adelaide, SA 5000, Australia.;Univ S Australia, Sansom Inst, Adelaide, SA 5000, Australia.;South Australian Hlth & Med Res Inst, Adelaide, SA 5000, Australia.;UCL Inst Child Hlth, Populat Policy & Practice, London WC1N 1EH, England..
    Iacono, William G.
    Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN 55455 USA..
    Jacobsson, Bo
    Sahlgrens Acad, Inst Clin Sci, Dept Obstet & Gynecol, S-41685 Gothenburg, Sweden.;Norwegian Inst Publ Hlth, Dept Genes & Environm, N-0403 Oslo, Norway..
    Jarvelin, Marjo-Riitta
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ Oulu, Fac Med, Ctr Life Course Epidemiol, Oulu 90014, Finland.;Oulu Univ Hosp, Unit Primary Care, Oulu 90029, Finland.;Univ Oulu, Bioctr Oulu, Oulu 90014, Finland..
    Jockel, Karl-Heinz
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, D-45147 Essen, Germany..
    Kaprio, Jaakko
    Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland.;THL Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland..
    Kardia, Sharon L. R.
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Lehtimaki, Terho
    Fimlab Labs, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Lehrer, Steven F.
    NYU Shanghai, Econ, Pudong 200122, Peoples R China.;Queens Univ, Policy Studies, Kingston, ON K7L 3N6, Canada..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld 4029, Australia..
    McGue, Matt
    Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN 55455 USA..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia..
    Pendleton, Neil
    Salford Royal Hosp, Inst Brain Behav & Mental Hlth, Ctr Clin & Cognit Neurosci, Manchester M6 8HD, Lancs, England.;Univ Manchester, Manchester Inst Collaborat Res Ageing, Manchester M13 9PL, Lancs, England..
    Penninx, Brenda W. J. H.
    Vrije Univ Amsterdam, Med Ctr, Psychiat, NL-1081 HL Amsterdam, Netherlands.;GGZ inGeest, NL-1081 HL Amsterdam, Netherlands..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.;THL Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland..
    Pirastu, Nicola
    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy..
    Pirastu, Mario
    Natl Res Council Italy, UOS Sassari, Ist Ric Genet & Biomed, I-07100 Sassari, Italy..
    Polasek, Ozren
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Split, Fac Med, Split 21000, Croatia..
    Posthuma, Danielle
    Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, NL-1081 HV Amsterdam, Netherlands..
    Power, Christine
    UCL Inst Child Hlth, Populat Policy & Practice, London WC1N 1EH, England..
    Province, Michael A.
    Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63018 USA..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Gen Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Schlessinger, David
    NIA, Genet Lab, Baltimore, MD 21224 USA..
    Schmidt, Reinhold
    Gen Hosp, Dept Neurol, A-8036 Graz, Austria.;Med Univ Graz, A-8036 Graz, Austria..
    Sorensen, Thorkild I. A.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, DK-2100 Copenhagen, Denmark.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.;Bispebjerg Hosp, Inst Prevent Med, DK-2000 Frederiksberg, Denmark.;Frederiksberg Univ Hosp, Inst Prevent Med, DK-2000 Frederiksberg, Denmark..
    Spector, Tim D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Stefansson, Kari
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Thurik, A. Roy
    Erasmus Univ, Erasmus Sch Econ, Dept Appl Econ, NL-3062 PA Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, NL-3062 PA Rotterdam, Netherlands.;Montpellier Business Sch, F-34080 Montpellier, France.;Panteia, NL-2715 CA Zoetermeer, Netherlands..
    Timpson, Nicholas J.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Tiemeier, Henning
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Psychiat, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Child & Adolescent Psychiat, NL-3015 GE Rotterdam, Netherlands..
    Tung, Joyce Y.
    23andMe Inc, Mountain View, CA 94041 USA..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Vollenweider, Peter
    Lausanne Univ Hosp CHUV, Dept Internal Med, Internal Med, CH-1011 Lausanne, Switzerland..
    Weir, David R.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48109 USA..
    Wilson, James F.
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.;Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Wright, Alan F.
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Conley, Dalton C.
    NYU, Dept Sociol, 550 1St Ave, New York, NY 10012 USA.;NYU, Sch Med, 550 1St Ave, New York, NY 10016 USA..
    Krueger, Robert F.
    Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN 55455 USA..
    Smith, George Davey
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Hofman, Albert
    Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA..
    Laibson, David I.
    Harvard Univ, Dept Econ, Cambridge, MA 02138 USA..
    Medland, Sarah E.
    QIMR Berghofer Med Res Inst, Quantitat Genet, Brisbane, Qld 4029, Australia..
    Meyer, Michelle N.
    Icahn Sch Med Mt Sinai, Grad Coll, Bioeth Program, Schenectady, NY 12308 USA..
    Yang, Jian
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.;Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4102, Australia..
    Johannesson, Magnus
    Stockholm Sch Econ, Dept Econ, S-11383 Stockholm, Sweden..
    Visscher, Peter M.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.;Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4102, Australia..
    Esko, Tonu
    Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.;Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA..
    Koellinger, Philipp D.
    Erasmus Univ, Inst Behav & Biol, NL-3062 PA Rotterdam, Netherlands.;Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands.;Univ Amsterdam, Amsterdam Business Sch, NL-1018 TV Amsterdam, Netherlands..
    Cesarini, David
    NYU, Dept Econ, New York, NY 10003 USA.;Res Inst Ind Econ, S-10215 Stockholm, Sweden..
    Benjamin, Daniel J.
    Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA 90089 USA..
    Genome-wide association study identifies 74 loci associated with educational attainment2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 533, no 7604, 539-542 p.Article in journal (Refereed)
    Abstract [en]

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample(1,2) of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

  • 307.
    Olmeda, David
    et al.
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Cerezo-Wallis, Daniela
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Riveiro-Falkenbach, Erica
    Univ Complutense Madrid, Inst I 12, Hosp Univ Octubre 12, Med Sch,Dept Pathol, Madrid 28041, Spain..
    Pennacchi, Paula C.
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Contreras-Alcalde, Marta
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Ibarz, Nuria
    Spanish Natl Canc Res Ctr CNIO, Prote Unit, Biotechnol Programme, Madrid 28029, Spain..
    Cifdaloz, Metehan
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain.;Roche Innovat Ctr Munich, Roche Pharma Res & Early Dev, D-82377 Penzberg, Germany..
    Catena, Xavier
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Calvo, Tonantzin G.
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Canon, Estela
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Alonso-Curbelo, Direna
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain.;Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA..
    Suarez, Javier
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Osterloh, Lisa
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Grana, Osvaldo
    Spanish Natl Canc Res Ctr CNIO, Bioinformat Unit, Struct Biol & Biocomp Programme, Madrid 28029, Spain..
    Mulero, Francisca
    Spanish Natl Canc Res Ctr CNIO, Mol Imaging Unit, Biotechnol Programme, Madrid 28029, Spain..
    Megias, Diego
    Spanish Natl Canc Res Ctr CNIO, Confocal Microscopy Unit, Biotechnol Programme, Madrid 28029, Spain..
    Canamero, Marta
    Spanish Natl Canc Res Ctr CNIO, Histopathol Unit, Biotechnol Programme, Madrid 28029, Spain..
    Martinez-Torrecuadrada, Jorge L.
    Spanish Natl Canc Res Ctr CNIO, Crystallog & Prot Engn Unit, Biotechnol Programme, Madrid 28029, Spain..
    Mondal, Chandrani
    Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Hematol & Oncol, Dept Med, New York, NY 10029 USA..
    Di Martino, Julie
    Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Hematol & Oncol, Dept Med, New York, NY 10029 USA..
    Lora, David
    Hosp Univ 12 Octubre, Inst I 12, CIBERESP, Madrid 28041, Spain..
    Martinez-Corral, Ines
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Spanish Natl Canc Res Ctr CNIO, Transgen Mice Unit, Biotechnol Programme, Madrid 28029, Spain.
    Bravo-Cordero, J. Javier
    Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Hematol & Oncol, Dept Med, New York, NY 10029 USA..
    Munoz, Javier
    Spanish Natl Canc Res Ctr CNIO, Prote Unit, Biotechnol Programme, Madrid 28029, Spain..
    Puig, Susana
    Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Melanoma Unit, Dermatol Dept, E-08036 Barcelona, Spain..
    Ortiz-Romero, Pablo
    Univ Complutense Madrid, Hosp Univ Octubre 12, Inst I 12, Dept Dermatol,Med Sch, Madrid 28041, Spain..
    Rodriguez-Peralto, Jose L.
    Univ Complutense Madrid, Inst I 12, Hosp Univ Octubre 12, Med Sch,Dept Pathol, Madrid 28041, Spain..
    Ortega, Sagrario
    Spanish Natl Canc Res Ctr CNIO, Transgen Mice Unit, Biotechnol Programme, Madrid 28029, Spain..
    Soengas, Maria S.
    Spanish Natl Canc Res Ctr CNIO, Melanoma Lab, Mol Oncol Programme, Madrid 28029, Spain..
    Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 546, no 7660, 676-680 p.Article in journal (Refereed)
    Abstract [en]

    Cutaneous melanoma is a type of cancer with an inherent potential for lymph node colonization, which is generally preceded by neolymphangiogenesis(1-3). However, sentinel lymph node removal does not necessarily extend the overall survival of patients with melanoma(4,5). Moreover, lymphatic vessels collapse and become dysfunctional as melanomas progress(6,7). Therefore, it is unclear whether (and how) lymphangiogenesis contributes to visceral metastasis. Soluble and vesicle-associated proteins secreted by tumours and/or their stroma have been proposed to condition pre-metastatic sites in patients with melanoma(8-14). Still, the identities and prognostic value of lymphangiogenic mediators remain unclear(2,14). Moreover, our understanding of lymphangiogenesis (in melanomas and other tumour types) is limited by the paucity of mouse models for live imaging of distal pre-metastatic niches(15). Injectable lymphatic tracers have been developed(7), but their limited diffusion precludes whole-body imaging at visceral sites(16). Vascular endothelial growth factor receptor 3 (VEGFR3) is an attractive 'lymphoreporter' 17 because its expression is strongly downregulated in normal adult lymphatic endothelial cells, but is activated in pathological situations such as inflammation and cancer(17,18). Here, we exploit this inducibility of VEGFR3 to engineer mouse melanoma models for whole-body imaging of metastasis generated by human cells, clinical biopsies or endogenously deregulated oncogenic pathways. This strategy revealed early induction of distal pre-metastatic niches uncoupled from lymphangiogenesis at primary lesions. Analyses of the melanoma secretome and validation in clinical specimens showed that the heparin-binding factor midkine is a systemic inducer of neo-lymphangiogenesis that defines patient prognosis. This role of midkine was linked to a paracrine activation of the mTOR pathway in lymphatic endothelial cells. These data support the use of VEGFR3 reporter mice as a 'MetAlert' discovery platform for drivers and inhibitors of metastasis.

  • 308.
    Olson, Jonas
    KTH, School of Electrical Engineering (EES), Space and Plasma Physics.
    The magnetospheric clock of Saturn: a self-organized plasma dynamoIn: Nature, ISSN 0028-0836, E-ISSN 1476-4687Article in journal (Other academic)
  • 309.
    Olsén, Arne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Jonsson, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Normark, Staffan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Fibronectin binding mediated by a novel class of surface organelles on Escherichia coli1989In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 338, no 6217, 652-5 p.Article in journal (Refereed)
    Abstract [en]

    Gram-negative bacteria are known to produce two types of surface organelles: flagella, which are required for motility and chemotaxis, and pili (fimbriae), which play a part in the interaction of bacteria with other bacteria and with eukaryotic host cells. Here we report a third class of E. coli surface organelles for which we propose the name curli. Curli are coiled surface structures composed of a single type of subunit, the curlin, which differs from all known pilin proteins and is synthesized in the absence of a cleavable signal peptide. Although the gene encoding this structural subunit, crl, is present and transcribed in most natural isolates of E. coli, only certain strains are able to assemble the subunit protein into curli. This assembly process occurs preferentially at growth temperatures below 37 degrees C. The ability of curli to mediate binding to fibronectin may be a virulence-associated property for wound colonization and for the colonization of fibronectin-coated surfaces.

  • 310. Orlando, Ludovic
    et al.
    Ginolhac, Aurelien
    Zhang, Guojie
    Froese, Duane
    Albrechtsen, Anders
    Stiller, Mathias
    Schubert, Mikkel
    Cappellini, Enrico
    Petersen, Bent
    Moltke, Ida
    Johnson, Philip L. F.
    Fumagalli, Matteo
    Vilstrup, Julia T.
    Raghavan, Maanasa
    Korneliussen, Thorfinn
    Malaspinas, Anna-Sapfo
    Vogt, Josef
    Szklarczyk, Damian
    Kelstrup, Christian D.
    Vinther, Jakob
    Dolocan, Andrei
    Stenderup, Jesper
    Velazquez, Amhed M. V.
    Cahill, James
    Rasmussen, Morten
    Wang, Xiaoli
    Min, Jiumeng
    Zazula, Grant D.
    Seguin-Orlando, Andaine
    Mortensen, Cecilie
    Magnussen, Kim
    Thompson, John F.
    Weinstock, Jacobo
    Gregersen, Kristian
    Roed, Knut H.
    Eisenmann, Vera
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Miller, Donald C.
    Antczak, Douglas F.
    Bertelsen, Mads F.
    Brunak, Soren
    Al-Rasheid, Khaled A. S.
    Ryder, Oliver
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mundy, John
    Krogh, Anders
    Gilbert, M. Thomas P.
    Kjaer, Kurt
    Sicheritz-Ponten, Thomas
    Jensen, Lars Juhl
    Olsen, Jesper V.
    Hofreiter, Michael
    Nielsen, Rasmus
    Shapiro, Beth
    Wang, Jun
    Willerslev, Eske
    Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 499, no 7456, 74-+ p.Article in journal (Refereed)
    Abstract [en]

    The rich fossil record of equids has made them a model for evolutionary processes(1). Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP)(2,3). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. prze-walskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus(4,5). We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population(6). We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.

  • 311.
    Pace, Michael L.
    et al.
    Institute of Ecosystem Studies, Millbrook, New York, USA.
    Cole, Jonathan J.
    Institute of Ecosystem Studies, Millbrook, New York, USA.
    Carpenter, Stephen R.
    Center for Limnology, University of Wisconsin, Madison, Wisconsin, USA.
    Kitchell, James F.
    Center for Limnology, University of Wisconsin, Madison, Wisconsin, USA.
    Hodgson, James R.
    Department of Biology, St. Norbert College, De Pere, Wisconsin, USA.
    Van de Bogert, Matthew C.
    Institute of Ecosystem Studies, Millbrook, New York, USA.
    Bade, Darren L.
    Center for Limnology, University of Wisconsin, Madison, Wisconsin, USA.
    Kritzberg, Emma S.
    Department of Ecology/Limnology, Lund University, Lund, Sweden.
    Bastviken, David
    Linköping University, Department of Thematic Studies, Department of Water and Environmental Studies. Linköping University, Faculty of Arts and Sciences.
    Whole-lake carbon-13 additions reveal terrestrial support of aquatic food webs2004In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 427, no 6971, 240-243 p.Article in journal (Refereed)
    Abstract [en]

    Ecosystems are supported by organic carbon from two distinct sources. Endogenous carbon is produced by photosynthesis within an ecosystem by autotrophic organisms. Exogenous carbon is produced elsewhere and transported into ecosystems. Consumers may use exogenous carbon with consequent influences on population dynamics, predator-prey relationships and ecosystem processes(1). For example, exogenous inputs provide resources that may enhance consumer abundance beyond levels supported by within-system primary production(2). Exogenous fluxes of organic carbon to ecosystems are often large, but this material is recalcitrant and difficult to assimilate, in contrast to endogenously produced organic matter, which is used more easily(3,4). Here we show, by the experimental manipulation of dissolved inorganic C-13 in two lakes, that internal primary production is insufficient to support the food webs of these ecosystems. Additions of NaH (CO3)-C-13 enriched the C-13 content of dissolved inorganic carbon, particulate organic carbon, zooplankton and fish. Dynamics of C-13 indicate that 40-55% of particulate organic carbon and 22-50% of zooplankton carbon are derived from terrestrial sources, showing that there is significant subsidy of these ecosystems by organic carbon produced outside their boundaries.

  • 312. Pagani, Mark
    et al.
    Pedentchouk, Nikolai
    Huber, Matthew
    Sluijs, Appy
    Schouten, Stefan
    Brinkhuis, Henk
    Damste, Jaap S. Sinninghe
    Dickens, Gerald R.
    Scientists, Expedit 302
    Arctic hydrology during global warming at the Palaeocene/Eocene thermal maximum2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 442, no 7103, 671-675 p.Article in journal (Refereed)
    Abstract [en]

    The Palaeocene/ Eocene thermal maximum represents a period of rapid, extreme global warming similar to 55 million years ago, superimposed on an already warm world(1-3). This warming is associated with a severe shoaling of the ocean calcite compensation depth(4) and a > 2.5 per mil negative carbon isotope excursion in marine and soil carbonates(1-4). Together these observations indicate a massive release of C-13- depleted carbon(4) and greenhouse- gas-induced warming. Recently, sediments were recovered from the central Arctic Ocean(5), providing the first opportunity to evaluate the environmental response at the North Pole at this time. Here we present stable hydrogen and carbon isotope measurements of terrestrial- plant- and aquatic- derived n- alkanes that record changes in hydrology, including surface water salinity and precipitation, and the global carbon cycle. Hydrogen isotope records are interpreted as documenting decreased rainout during moisture transport from lower latitudes and increased moisture delivery to the Arctic at the onset of the Palaeocene/ Eocene thermal maximum, consistent with predictions of poleward storm track migrations during global warming(6). The terrestrial- plant carbon isotope excursion ( about -4.5 to -6 per mil) is substantially larger than those of marine carbonates. Previously, this offset was explained by the physiological response of plants to increases in surface humidity(2). But this mechanism is not an effective explanation in this wet Arctic setting, leading us to hypothesize that the true magnitude of the excursion - and associated carbon input was greater than originally surmised. Greater carbon release and strong hydrological cycle feedbacks may help explain the maintenance of this unprecedented warmth.

  • 313. Palmer, T N
    et al.
    Räisänen, Jouni
    SMHI, Research Department, Climate research - Rossby Centre.
    Quantifying the risk of extreme seasonal precipitation events in a changing climate2002In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 415, no 6871, 512-514 p.Article in journal (Refereed)
    Abstract [en]

    Increasing concentrations of atmospheric carbon dioxide will almost certainly lead to changes in global mean climate(1). But because-by definition-extreme events are rare, it is significantly more difficult to quantify the risk of extremes. Ensemble-based probabilistic predictions(2), as used in short- and medium-term forecasts of weather and climate, are more useful than deterministic forecasts using a 'best guess' scenario to address this sort of problem(3,4). Here we present a probabilistic analysis of 19 global climate model simulations with a generic binary decision model. We estimate that the probability of total boreal winter precipitation exceeding two standard deviations above normal will increase by a factor of five over parts of the UK over the next 100 years. We find similar increases in probability for the Asian monsoon region in boreal summer, with implications for flooding in Bangladesh. Further practical applications of our techniques would be helped by the use of larger ensembles (for a more complete sampling of model uncertainty) and a wider range of scenarios at a resolution adequate to analyse average-size river basins.

  • 314.
    Pangala, Sunitha R.
    et al.
    Open University, England; University of Lancaster, England.
    Enrich Prast, Alex
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. University of Federal Rio de Janeiro, Brazil.
    Basso, Luana S.
    IPEN, Brazil.
    Bittencourt Peixoto, Roberta
    University of Federal Rio de Janeiro, Brazil.
    Bastviken, David
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Hornibrook, Edward R. C.
    University of Bristol, England; University of British Columbia, Canada.
    Gatti, Luciana V.
    IPEN, Brazil; National Institute Space Research INPE, Brazil.
    Marotta, Humberto
    University of Federal Fluminense, Brazil.
    Silva Braucks Calazans, Luana
    University of Federal Rio de Janeiro, Brazil.
    Monica Sakuragui, Cassia
    University of Federal Rio de Janeiro, Brazil.
    Rodrigues Bastos, Wanderley
    Federal University of Rondonia, Brazil.
    Malm, Olaf
    University of Federal Rio de Janeiro, Brazil.
    Gloor, Emanuel
    University of Leeds, England.
    Bharat Miller, John
    NOAA, CO 80305 USA.
    Gauci, Vincent
    Open University, England.
    Large emissions from floodplain trees close the Amazon methane budget2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 552, no 7684, 230-+ p.Article in journal (Refereed)
    Abstract [en]

    Wetlands are the largest global source of atmospheric methane (CH4)(1), a potent greenhouse gas. However, methane emission inventories from the Amazon floodplain(2,3), the largest natural geographic source of CH4 in the tropics, consistently underestimate the atmospheric burden of CH4 determined via remote sensing and inversion modelling(4,5), pointing to a major gap in our understanding of the contribution of these ecosystems to CH4 emissions. Here we report CH4 fluxes from the stems of 2,357 individual Amazonian floodplain trees from 13 locations across the central Amazon basin. We find that escape of soil gas through wetland trees is the dominant source of regional CH4 emissions. Methane fluxes from Amazon tree stems were up to 200 times larger than emissions reported for temperate wet forests(6) and tropical peat swamp forests(7), representing the largest non-ebullitive wetland fluxes observed. Emissions from trees had an average stable carbon isotope value (delta C-13) of -66.2 +/- 6.4 per mil, consistent with a soil biogenic origin. We estimate that floodplain trees emit 15.1 +/- 1.8 to 21.2 +/- 2.5 teragrams of CH4 a year, in addition to the 20.5 +/- 5.3 teragrams a year emitted regionally from other sources. Furthermore, we provide a topdown regional estimate of CH4 emissions of 42.7 +/- 5.6 teragrams of CH4 a year for the Amazon basin, based on regular vertical lower-troposphere CH4 profiles covering the period 2010-2013. We find close agreement between our top-down and combined bottom-up estimates, indicating that large CH4 emissions from trees adapted to permanent or seasonal inundation can account for the emission source that is required to close the Amazon CH4 budget. Our findings demonstrate the importance of tree stem surfaces in mediating approximately half of all wetland CH4 emissions in the Amazon floodplain, a region that represents up to one-third of the global wetland CH4 source when trees are combined with other emission sources.

  • 315.
    Pardo, Jason D.
    et al.
    Univ Calgary, Dept Comparat Biol & Expt Med, 3330 Hosp Dr, Calgary, AB T2N 4N1, Canada..
    Szostakiwskyj, Matt
    Univ Calgary, Dept Biol Sci, 2500 Univ Dr, Calgary, AB T2N 1N4, Canada..
    Ahlberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Anderson, Jason S.
    Univ Calgary, Dept Comparat Biol & Expt Med, 3330 Hosp Dr, Calgary, AB T2N 4N1, Canada..
    Hidden morphological diversity among early tetrapods2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 546, no 7660, 642-645 p.Article in journal (Refereed)
    Abstract [en]

    Phylogenetic analysis of early tetrapod evolution has resulted in a consensus across diverse data sets(1-3) in which the tetrapod stem group is a relatively homogenous collection of medium-to large-sized animals showing a progressive loss of 'fish' characters as they become increasingly terrestrial(4,5), whereas the crown group demonstrates marked morphological diversity and disparity(6). The oldest fossil attributed to the tetrapod crown group is the highly specialized astopod Lethiscus stocki(7,8), which shows a small size, extreme axial elongation, loss of limbs, spool-shaped vertebral centra, and a skull with reduced centres of ossification, in common with an otherwise disparate group of small animals known as lepospondyls. Here we use micro-computed tomography of the only known specimen of Lethiscus to provide new information that strongly challenges this consensus. Digital dissection reveals extremely primitive cranial morphology, including a spiracular notch, a large remnant of the notochord within the braincase, an open ventral cranial fissure, an anteriorly restricted parasphenoid element, and Meckelian ossifications. The braincase is elongate and lies atop a dorsally projecting septum of the parasphenoid bone, similar to stem tetrapods such as embolomeres. This morphology is consistent in a second astopod, Coloraderpeton, although the details differ. Phylogenetic analysis, including critical new braincase data, places astopods deep on the tetrapod stem, whereas another major lepospondyl lineage is displaced into the amniotes. These results show that stem group tetrapods were much more diverse in their body plans than previously thought. Our study requires a change in commonly used calibration dates for molecular analyses, and emphasizes the importance of character sampling for early tetrapod evolutionary relationships.

  • 316.
    Parmesan, Camille
    et al.
    University of Austin.
    Ryrholm, Nils
    Uppsala Universitet.
    Stefanescu, Constanti
    Catalan Butterfly Monitoring Scheme.
    Hill, Jane
    University of Durham.
    Thomas, Cris
    University of Leeds.
    Descimon, Henri
    Universite´ de Provence.
    Huntley, Brian
    University of Durham.
    Kaila, Lauri
    University of Helsinki.
    Kullberg, Jaakko
    University of Helsinki.
    Tammaru, Toomas
    Estonian Agricultural University.
    Tennent, John
    British Natural History Museum.
    Thomas, Jeremy
    Warren, marrtin
    Butterfly Conservation UK.
    Poleward shifts in geographical ranges of butterfly species associated with regionalwarming1999In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 399, no 6736, 579-583 p.Article in journal (Refereed)
    Abstract [en]

    Mean global temperatures have risen this century, and further warming is predicted to continue for the next 50–100 years. Some migratory species can respond rapidly to yearly climate variation by altering the timing or destination of migration, but most wildlife is sedentary and so is incapable of such a rapid response. For these species, responses to the warming trend should be slower, reflected in poleward shifts of the range. Such changes in distribution would occur at the level of the population, stemming not from changes in the pattern of individuals' movements, but from changes in the ratios of extinctions to colonizations at the northern and southern boundaries of the range. A northward range shift therefore occurs when there is net extinction at the southern boundary or net colonization at the northern boundary. However, previous evidence has been limited to a single species or to only a portion of the species' range. Here we provide the first large-scale evidence of poleward shifts in entire species' ranges. In a sample of 35 non-migratory European butterflies, 63% have ranges that have shifted to the north by 35–240 km during this century, and only 3% have shifted to the south.

  • 317. Pastorello, A.
    et al.
    Smartt, S. J.
    Mattila, S.
    Eldridge, J. J.
    Young, D.
    Itagaki, K.
    Yamaoka, H.
    Navasardyan, H.
    Valenti, S.
    Patat, F.
    Agnoletto, I.
    Augusteijn, T.
    Benetti, S.
    Cappellaro, E.
    Boles, T.
    Bonnet-Bidaud, J. -M
    Botticella, M. T.
    Bufano, F.
    Cao, C.
    Deng, J.
    Dennefeld, M.
    Elias-Rosa, N.
    Harutyunyan, A.
    Keenan, F. P.
    Iijima, T.
    Lorenzi, V.
    Mazzali, P. A.
    Meng, X.
    Nakano, S.
    Nielsen, T. B.
    Smoker, J. V.
    Stanishev, Vallery
    Stockholm University, Faculty of Science, Department of Physics.
    Turatto, M.
    Xu, D.
    Zampieri, L.
    A giant outburst two years before the core-collapse of a massive star2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 447, no 7146, 829-832 p.Article in journal (Refereed)
    Abstract [en]

    The death of massive stars produces a variety of supernovae, which are linked to the structure of the exploding stars(1,2). The detection of several precursor stars of type II supernovae has been reported ( see, for example, ref. 3), but we do not yet have direct information on the progenitors of the hydrogen-deficient type Ib and Ic supernovae. Here we report that the peculiar type Ib supernova SN 2006jc is spatially coincident with a bright optical transient(4) that occurred in 2004. Spectroscopic and photometric monitoring of the supernova leads us to suggest that the progenitor was a carbon-oxygen Wolf - Rayet star embedded within a helium-rich circumstellar medium. There are different possible explanations for this pre-explosion transient. It appears similar to the giant outbursts of luminous blue variable stars (LBVs) of 60 - 100 solar masses(5), but the progenitor of SN 2006jc was helium- and hydrogen-deficient ( unlike LBVs). An LBV-like outburst of a Wolf - Rayet star could be invoked, but this would be the first observational evidence of such a phenomenon. Alternatively, a massive binary system composed of an LBV that erupted in 2004, and a Wolf - Rayet star exploding as SN 2006jc, could explain the observations.

  • 318. Paul, Jan
    CO dissociation on potassium promoted aluminum1986In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 323, 701-703 p.Article in journal (Refereed)
  • 319.
    Pedersen, Helle Krogh
    et al.
    Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
    Gudmundsdottir, Valborg
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark.
    Nielsen, Henrik Bjorn
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology. Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; VTT Technical Research Centre of Finland, Espoo, Finland.
    Nielsen, Trine
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Jensen, Benjamin A. H.
    Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
    Forslund, Kristoffer
    European Molecular Biology Laboratory, Heidelberg, Germany.
    Hildebrand, Falk
    European Molecular Biology Laboratory, Heidelberg, Germany; Department of Bioscience Engineering, Vrije Universiteit Brussel, Brussels, Belgium; Center for the Biology of Disease, VIB, Leuven, Belgium.
    Prifti, Edi
    MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France; Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
    Falony, Gwen
    Center for the Biology of Disease, VIB, Leuven, Belgium; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
    Le Chatelier, Emmanuelle
    MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France.
    Levenez, Florence
    MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France.
    Dore, Joel
    MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France; Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
    Mattila, Ismo
    VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center, Gentofte, Denmark.
    Plichta, Damian R.
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark.
    Pöhö, Paivi
    VTT Technical Research Centre of Finland, Espoo, Finland; Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
    Hellgren, Lars I.
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark.
    Arumugam, Manimozhiyan
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Sunagawa, Shinichi
    European Molecular Biology Laboratory, Heidelberg, Germany; nstitute of Microbiology, ETH Zurich, Zurich, Switzerland.
    Vieira-Silva, Sara
    Center for the Biology of Disease, VIB, Leuven, Belgium; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
    Jørgensen, Torben
    Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Research Centre for Prevention and Health, Centre for Health, Capital Region, Glostrup Hospital, Glostrup, Denmark.
    Holm, Jacob Bak
    Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
    Trost, Kajetan
    Steno Diabetes Center, Gentofte, Denmark.
    Kristiansen, Karsten
    Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China.
    Brix, Susanne
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark.
    Raes, Jeroen
    Department of Bioscience Engineering, Vrije Universiteit Brussel, Brussels, Belgium; Center for the Biology of Disease, VIB, Leuven, Belgium; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
    Wang, Jun
    Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China; Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Macau University of Science and Technology, Avenida Wai long, Taipa, Macau; Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, Hong Kong.
    Hansen, Torben
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
    Bork, Peer
    European Molecular Biology Laboratory, Heidelberg, Germany; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany; Max Delbrück Centre for Molecular Medicine, Berlin, Germany; Department of Bioinformatics, University of Wuerzburg, Würzburg, Germany.
    Brunak, Søren
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark; Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Oresic, Matej
    Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center, Gentofte, Denmark.
    Ehrlich, S. Dusko
    MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France; King's College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, London, United Kingdom.
    Pedersen, Oluf
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Human gut microbes impact host serum metabolome and insulin sensitivity2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 535, no 7612, 376-+ p.Article in journal (Refereed)
    Abstract [en]

    Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.

  • 320.
    Pedersen, Kai O.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy, Mathematics and Science Section.
    Sedimentation equilibrium measurements with low molecular substances in the ultra-centrifuge1935In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 135, 304-305 p.Article in journal (Refereed)
    Abstract [en]

    The calculated molecular weights agreed fairly well with the known values for these substances except in the cases of the substance with the lowest molecular weight, CsCl, where the difference in concentration was very small. Quite recently, Prof. Svedberg has greatly improved his ultra-centrifuge (see Svedberg, loc.

  • 321.
    Pedersen, Kai O.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy, Mathematics and Science Section.
    Temperature stability and denaturation of serum albumin1931In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 128, 150-151 p.Article in journal (Refereed)
    Abstract [en]

    It has been shown by Svedberg and Sjögren1 that at ordinary temperature serum albumin is stable (that is, homogeneous with regard to molecular weight) in a region of pH varying between 4 and 9. These authors have also shown that outside of the stability region, but not too far from it, the serum albumin molecule is dissociated into smaller molecules. This first stage of breaking up of the molecule probably means the formation of particles of half the weight of the original molecule. The complete breaking up of the molecule follows immediately after this stage. The first stage has been shown to be reversible with regard to the molecular weight.

  • 322. Percec, V.
    et al.
    Dulcey, A. E.
    Balagurusamy, V. S. K.
    Miura, Y.
    Smidrkal, J.
    Peterca, M.
    Nummelin, S.
    Edlund, Ulrica
    KTH, Superseded Departments, Polymer Technology.
    Hudson, S. D.
    Heiney, P. A.
    Hu, D. A.
    Magonov, S. N.
    Vinogradov, S. A.
    Self-assembly of amphiphilic dendritic dipeptides into helical pores2004In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 430, no 7001, 764-768 p.Article in journal (Refereed)
    Abstract [en]

    Natural pore-forming proteins act as viral helical coats(1) and transmembrane channels(2-4), exhibit antibacterial activity(5) and are used in synthetic systems, such as for reversible encapsulation(6) or stochastic sensing(7). These diverse functions are intimately linked to protein structure(1-4). The close link between protein structure and protein function makes the design of synthetic mimics a formidable challenge, given that structure formation needs to be carefully controlled on all hierarchy levels, in solution and in the bulk. In fact, with few exceptions(8,9), synthetic pore structures capable of assembling into periodically ordered assemblies that are stable in solution and in the solid state(10-13) have not yet been realized. In the case of dendrimers, covalent(14) and non- covalent(15) coating and assembly of a range of different structures(15-17) has only yielded closed columns(18). Here we describe a library of amphiphilic dendritic dipeptides that self-assemble in solution and in bulk through a complex recognition process into helical pores. We find that the molecular recognition and self-assembly process is sufficiently robust to tolerate a range of modifications to the amphiphile structure, while preliminary proton transport measurements establish that the pores are functional. We expect that this class of self-assembling dendrimers will allow the design of a variety of biologically inspired systems with functional properties arising from their porous structure.

  • 323.
    Perk, Joep
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences.
    PERSPECTIVE The power of disease prevention2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 493, no 7434, S6-S6 p.Article in journal (Other academic)
  • 324. Perricaudet, Michel
    et al.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Microbiology.
    Virtanen, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Microbiology.
    Pettersson, Ulf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Microbiology.
    Structure of two spliced mRNAs from the transforming region of human subgroup C adenoviruses1979In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 281, no 5733, 694-696 p.Article in journal (Other academic)
    Abstract [en]

    The papova viruses and the human adenoviruses are widely used as a model system to study cell transformation in vitro. In subgroup C human adenoviruses, fragment HpaI-E, which comprises as little as 4.5% of the adenovirus type 5 (ad5) DNA, is sufficient for transformation of rat embryo cells1. Analysis of messenger RNAs (mRNAs) from the transforming region of adenoviruses type 2 (ad2) has identified several spliced mRN A species2−4. Promoter mapping studies indicate that the leftmost early region contains two separate transcription units, E1A and E1B (ref. 5) (Fig. 1a). Region E1A is approximately equivalent HpaI-E. The complete nucleotide sequence of the HpaI-E fragment of ad5 was recently reported6. However, the spliced nature of early adenovirus mRNAs prevents a prediction of the amino acid sequence of the corresponding polypeptides directly from the DNA sequence. To study the structure of early ad2 mRNAs at the nucleotide level, we have used molecular cloning procedures to amplify the appropriate mRNA sequences. In this report, clones corresponding to the 12S and 13S mRNA from region E1A (Fig. 1c) have been isolated and characterised by hybridisation and sequence analysis. Our results enable us to predict the primary sequence of two related polypeptides from region E1A of human subgroup C adenoviruses.

  • 325. Perry, John R. B.
    et al.
    Day, Felix
    Elks, Cathy E.
    Sulem, Patrick
    Thompson, Deborah J.
    Ferreira, Teresa
    He, Chunyan
    Chasman, Daniel I.
    Esko, Toenu
    Thorleifsson, Gudmar
    Albrecht, Eva
    Ang, Wei Q.
    Corre, Tanguy
    Cousminer, Diana L.
    Feenstra, Bjarke
    Franceschini, Nora
    Ganna, Andrea
    Johnson, Andrew D.
    Kjellqvist, Sanela
    Lunetta, Kathryn L.
    McMahon, George
    Nolte, Ilja M.
    Paternoster, Lavinia
    Porcu, Eleonora
    Smith, Albert V.
    Stolk, Lisette
    Teumer, Alexander
    Tsernikova, Natalia
    Tikkanen, Emmi
    Ulivi, Sheila
    Wagner, Erin K.
    Amin, Najaf
    Bierut, Laura J.
    Byrne, Enda M.
    Hottenga, Jouke-Jan
    Koller, Daniel L.
    Mangino, Massimo
    Pers, Tune H.
    Yerges-Armstrong, Laura M.
    Zhao, Jing Hua
    Andrulis, Irene L.
    Anton-Culver, Hoda
    Atsma, Femke
    Bandinelli, Stefania
    Beckmann, Matthias W.
    Benitez, Javier
    Blomqvist, Carl
    Bojesen, Stig E.
    Bolla, Manjeet K.
    Bonanni, Bernardo
    Brauch, Hiltrud
    Brenner, Hermann
    Buring, Julie E.
    Chang-Claude, Jenny
    Chanock, Stephen
    Chen, Jinhui
    Chenevix-Trench, Georgia
    Collee, J. Margriet
    Couch, Fergus J.
    Couper, David
    Coviello, Andrea D.
    Cox, Angela
    Czene, Kamila
    D'adamo, Adamo Pio
    Smith, George Davey
    De Vivo, Immaculata
    Demerath, Ellen W.
    Dennis, Joe
    Devilee, Peter
    Dieffenbach, Aida K.
    Dunning, Alison M.
    Eiriksdottir, Gudny
    Eriksson, Johan G.
    Fasching, Peter A.
    Ferrucci, Luigi
    Flesch-Janys, Dieter
    Flyger, Henrik
    Foroud, Tatiana
    Franke, Lude
    Garcia, Melissa E.
    Garcia-Closas, Montserrat
    Geller, Frank
    de Geus, Eco E. J.
    Giles, Graham G.
    Gudbjartsson, Daniel F.
    Gudnason, Vilmundur
    Guenel, Pascal
    Guo, Suiqun
    Hall, Per
    Hamann, Ute
    Haring, Robin
    Hartman, Catharina A.
    Heath, AndrewC.
    Hofman, Albert
    Hooning, Maartje J.
    Hopper, John L.
    Hu, Frank B.
    Hunter, David J.
    Karasik, David
    Kiel, Douglas P.
    Knight, Julia A.
    Kosma, Veli-Matti
    Kutalik, Zoltan
    Lai, Sandra
    Lambrechts, Diether
    Lindblom, Annika
    Maegi, Reedik
    Magnusson, Patrik K.
    Mannermaa, Arto
    Martin, Nicholas G.
    Masson, Gisli
    McArdle, Patrick F.
    McArdle, Wendy L.
    Melbye, Mads
    Michailidou, Kyriaki
    Mihailov, Evelin
    Milani, Lili
    Milne, Roger L.
    Nevanlinna, Heli
    Neven, Patrick
    Nohr, Ellen A.
    Oldehinkel, Albertine J.
    Oostra, Ben A.
    Palotie, Aarno
    Peacock, Munro
    Pedersen, Nancy L.
    Peterlongo, Paolo
    Peto, Julian
    Pharoah, Paul D. P.
    Postma, Dirkje S.
    Pouta, Anneli
    Pylkaes, Katri
    Radice, Paolo
    Ring, Susan
    Rivadeneira, Fernando
    Robino, Antonietta
    Rose, Lynda M.
    Rudolph, Anja
    Salomaa, Veikko
    Sanna, Serena
    Schlessinger, David
    Schmidt, Marjanka K.
    Southey, Mellissa C.
    Sovio, Ulla
    Stampfer, Meir J.
    Stoeckl, Doris
    Storniolo, Anna M.
    Timpson, Nicholas J.
    Tyrer, Jonathan
    Visser, Jenny A.
    Vollenweider, Peter
    Voelzke, Henry
    Waeber, Gerard
    Waldenberger, Melanie
    Wallaschofski, Henri
    Wang, Qin
    Willemsen, Gonneke
    Winqvist, Robert
    Wolffenbuttel, Bruce H. R.
    Wright, Margaret J.
    Boomsma, Dorret I.
    Econs, Michael J.
    Khaw, Kay-Tee
    Loos, Ruth J. F.
    McCarthy, Mark I.
    Montgomery, Grant W.
    Rice, John P.
    Streeten, Elizabeth A.
    Thorsteinsdottir, Unnur
    van Duijn, Cornelia M.
    Alizadeh, Behrooz Z.
    Bergmann, Sven
    Boerwinkle, Eric
    Boyd, Heather A.
    Crisponi, Laura
    Gasparini, Paolo
    Gieger, Christian
    Harris, Tamara B.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jaervelin, Marjo-Riitta
    Kraft, Peter
    Lawlor, Debbie
    Metspalu, Andres
    Pennell, Craig E.
    Ridker, Paul M.
    Snieder, Harold
    Sorensen, Thorkild I. A.
    Spector, Tim D.
    Strachan, David P.
    Uitterlinden, Andre G.
    Wareham, Nicholas J.
    Widen, Elisabeth
    Zygmunt, Marek
    Murray, Anna
    Easton, Douglas F.
    Stefansson, Kari
    Murabito, Joanne M.
    Ong, Ken K.
    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 514, no 7520, 92-+ p.Article in journal (Refereed)
    Abstract [en]

    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-causemortality(1). Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation(2,3), but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

  • 326.
    Persson, A.
    et al.
    Linköping University Hospital, Sweden.
    Paterlini, M.
    Paterlini, M..
    Q&A: An insider's view of the body2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 455, no 7216, 1036 p.Other (Other academic)
    Abstract [en]

    [No abstract available]

  • 327. Petrie, M
    et al.
    Schwabl, H
    Brande-Lavridsen, Nanna
    Burke, T
    Maternal investment: Sex differences in avian yolk hormone levels2001In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 412, 498- p.Article in journal (Refereed)
    Abstract [en]

    It has been suggested that female birds put more resources into eggs fathered by attractive males by laying larger eggs1 or by adding more testosterone2, but this inference could be undermined if eggs of different sex are provisioned differently, as these studies did not control for sex differences. Here we compare hormone concentrations in the yolks of male and female eggs and find that these are significantly different. Our results indicate that it is premature to conclude that female birds invest more in eggs sired by a preferred male, and raise the possibility that yolk sex steroids may be part of the sex-determining process in birds.

  • 328. Philippe, Herve
    et al.
    Brinkmann, Henner
    Copley, Richard R.
    Moroz, Leonid L.
    Nakano, Hiroaki
    Poustka, Albert J.
    Wallberg, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Systematic Biology.
    Peterson, Kevin J.
    Telford, Maximilian J.
    Acoelomorph flatworms are deuterostomes related to Xenoturbella2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 470, no 7333, 255-260 p.Article in journal (Refereed)
    Abstract [en]

    Xenoturbellida and Acoelomorpha are marine worms with contentious ancestry. Both were originally associated with the flatworms (Platyhelminthes), but molecular data have revised their phylogenetic positions, generally linking Xenoturbellida to the deuterostomes(1,2) and positioning the Acoelomorpha as the most basally branching bilaterian group(s)(3-6). Recent phylogenomic data suggested that Xenoturbellida and Acoelomorpha are sister taxa and together constitute an early branch of Bilateria(7). Here we assemble three independent data sets-mitochondrial genes, a phylogenomic data set of 38,330 amino-acid positions and new microRNA (miRNA) complements-and show that the position of Acoelomorpha is strongly affected by a long-branch attraction (LBA) artefact. When we minimize LBA we find consistent support for a position of both acoelomorphs and Xenoturbella within the deuterostomes. The most likely phylogeny links Xenoturbella and Acoelomorpha in a clade we call Xenacoelomorpha. The Xenacoelomorpha is the sister group of the Ambulacraria (hemichordates and echinoderms). We show that analyses of miRNA complements(8) have been affected by character loss in the acoels and that both groups possess one miRNA and the gene Rsb66 otherwise specific to deuterostomes. In addition, Xenoturbella shares one miRNA with the ambulacrarians, and two with the acoels. This phylogeny makes sense of the shared characteristics of Xenoturbellida and Acoelomorpha, such as ciliary ultrastructure and diffuse nervous system, and implies the loss of various deuterostome characters in the Xenacoelomorpha including coelomic cavities, through gut and gill slits.

  • 329. Pierce, Stephanie E.
    et al.
    Ahlberg, Per E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Hutchinson, John R.
    Molnar, Julia L.
    Sanchez, Sophie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Tafforeau, Paul
    Clack, Jennifer A.
    Vertebral architecture in the earliest stem tetrapods2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 494, no 7436, 226-229 p.Article in journal (Refereed)
    Abstract [en]

    The construction of the vertebral column has been used as a key anatomical character in defining and diagnosing early tetrapod groups(1). Rhachitomous vertebrae(2)-in which there is a dorsally placed neural arch and spine, an anteroventially placed intercentrum and paired, posterodorsally placed pleurocentra have long been considered the ancestral morphology for tetrapods(1,3-6). Nonetheless, very little is known about vertebral anatomy in the earliest stem tetrapods, because most specimens remain trapped in surrounding matrix, obscuring Important anatomical features(7-9). Here we describe the three-dimensional vertebral architecture of the Late Devonian stem tetrapod Ichthyostega using propagation phase-contrast X-ray synchrotron. microtomography. Our scans reveal a diverse array of new morphological, and associated developmental and functional, characteristics, including a possible posterior-to-anterior vertebral ossification sequence and the first evolutionary appearance of ossified sternal elements. One of the most intriguing features relates to the positional relationships between the vertebral elements, with the pleurocentra being unexpectedly sutured or fused to the intercentra that directly succeed them, indicating a 'reverse' rhachitomous design(10). Comparison of Ichthyostega with two other stem tetrapods, Acanthostegi and Pederpess, shows that reverse rhachitomous vertebrae may be the ancestral condition for limbed vertebrates. This study fundamentally revises our current understanding' of vertebral column evolution in the earliest tetrapods and raises questions about the presumed vertebral architecture of tetrapodomorph fish(12,13) and later, more crownward, tetrapods.

  • 330.
    Pizzari, T
    et al.
    Department of Animal Environment & Health, Swedish University of Agricultural Science.
    Cornwallis, C K
    Department of Animal & Plant Sciences, University of Sheffield.
    Lovlie, H
    Stockholm University, Faculty of Science, Department of Zoology, Department of Ethology.
    Jakobsson, S
    Stockholm University, Faculty of Science, Department of Zoology, Department of Ethology.
    Birkhead, T R
    Department of Animal & Plant Sciences, University of Sheffield.
    Sophisticated sperm allocation in male fowl2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 426, 70-74 p.Article in journal (Refereed)
  • 331.
    Pizzari, Tommaso
    et al.
    Swedish University of Agricultural Sciences, Skara, Sweden.
    Cornwallis, Charles K.
    University of Sheffield, UK.
    Løvlie, Hanne
    Stockholm University, Sweden.
    Jakobsson, Sven
    Stockholm University, Sweden.
    Birkhead, Tim R.
    University of Sheffield, UK.
    Sophisticated sperm allocation in male fowl2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 426, 70-74 p.Article in journal (Refereed)
    Abstract [en]

    When a female is sexually promiscuous, the ejaculates of different males compete for the fertilization of her eggs; the more sperm a male inseminates into a female, the more likely he is to fertilize her eggs. Because sperm production is limited and costly, theory predicts that males will strategically allocate sperm (1) according to female promiscuity, (2) saving some for copulations with new females, and (3) to females producing more and/or better offspring. Whether males allocate sperm in all of these ways is not known, particularly in birds where the collection of natural ejaculates only recently became possible. Here we demonstrate male sperm allocation of unprecedented sophistication in the fowl Gallus gallus. Males show status-dependent sperm investment in females according to the level of female promiscuity; they progressively reduce sperm investment in a particular female but, on encountering a new female, instantaneously increase their sperm investment; and they preferentially allocate sperm to females with large sexual ornaments signalling superior maternal investment. Our results indicate that female promiscuity leads to the evolution of sophisticated male sexual behaviour.

  • 332. Porter, John R.
    et al.
    Deutsch, Lisa
    Stockholm University, Stockholm Resilience Centre.
    Dumaresq, David
    Dyball, Rob
    How will growing cities eat?2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 469, no 7328, 34-34 p.Article in journal (Refereed)
  • 333. Pose, David
    et al.
    Verhage, Leonie
    Ott, Felix
    Yant, Levi
    Mathieu, Johannes
    Angenent, Gerco C.
    Immink, Richard G. H.
    Schmid, Markus
    Max Planck Institute for Developmental Biology, Department of Molecular Biology, Spemannstrasse 35, 72076 Tübingen, Germany.
    Temperature-dependent regulation of flowering by antagonistic FLM variants2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 503, no 7476, 414-+ p.Article in journal (Refereed)
  • 334. Price, Trevor D.
    et al.
    Hooper, Daniel M.
    Buchanan, Caitlyn D.
    Johansson, Ulf S.
    Swedish Museum of Natural History, Department of Zoology.
    Tietze, D. Thomas
    Alström, Per
    Olsson, Urban
    Ghosh-Harihar, Mousumi
    Ishtiaq, Farah
    Gupta, Sandeep K.
    Martens, Jochen
    Harr, Bettina
    Singh, Pratap
    Mohan, Dhananjai
    Niche filling slows the diversification of Himalayan songbirds2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 509, 222-225 p.Article in journal (Refereed)
  • 335.
    Pruszynski, J. Andrew
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Queen’s University, Kingston, Ontario.
    Kurtzer, Isaac
    New York College of Osteopathic Medicine, Queen’s University, Kingston, Ontario, New York College of Osteopathic Medicine, Old Westbury, New York.
    Nashed, Joseph Y.
    Queen’s University, Kingston, Ontario.
    Omrani, Mohsen
    Queen’s University, Kingston, Ontario.
    Brouwer, Brenda
    Queen’s University, Kingston, Ontario.
    Scott, Stephen H.
    Queen’s University, Kingston, Ontario.
    Primary motor cortex underlies multi-joint integration for fast feedback control2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 478, no 7369, 387-390 p.Article in journal (Refereed)
    Abstract [en]

    A basic difficulty for the nervous system is integrating locally ambiguous sensory information to form accurate perceptions about the outside world(1-4). This local-to-global problem is also fundamental to motor control of the arm, because complex mechanical interactions between shoulder and elbow allow a particular amount of motion at one joint to arise from an infinite combination of shoulder and elbow torques(5). Here we show, in humans and rhesus monkeys, that a transcortical pathway through primary motor cortex (M1) resolves this ambiguity during fast feedback control. We demonstrate that single M1 neurons of behaving monkeys can integrate shoulder and elbow motion information into motor commands that appropriately counter the underlying torque within about 50 milliseconds of a mechanical perturbation. Moreover, we reveal a causal link between M1 processing and multi-joint integration in humans by showing that shoulder muscle responses occurring 50 milliseconds after pure elbow displacement can be potentiated by transcranial magnetic stimulation. Taken together, our results show that transcortical processing through M1 permits feedback responses to express a level of sophistication that rivals voluntary control; this provides neurophysiological support for influential theories positing that voluntary movement is generated by the intelligent manipulation of sensory feedback(6,7).

  • 336. Purcell, Shaun M.
    et al.
    Wray, R
    Stone, L
    Visscher, M
    O'Donovan, C
    Sullivan, F
    Sklar, Pamela
    Ruderfer, M
    McQuillin, Andrew
    Morris, W
    O'Dushlaine, T
    Corvin, Aiden
    Holmans, A
    Macgregor, Stuart
    Gurling, Hugh
    Blackwood, R
    Craddock, J
    Gill, Michael
    Hultman, Christina M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Kirov, K
    Lichtenstein, Paul
    Muir, J
    Owen, J
    Pato, N
    Scolnick, M
    St Clair, David
    Williams, M
    Georgieva, Lyudmila
    Nikolov, Ivan
    Norton, N
    Williams, H
    Toncheva, Draga
    Milanova, Vihra
    Thelander, F
    Sullivan, Patrick
    Kenny, Elaine
    Quinn, M
    Choudhury, Khalid
    Datta, Susmita
    Pimm, Jonathan
    Thirumalai, Srinivasa
    Puri, Vinay
    Krasucki, Robert
    Lawrence, Jacob
    Quested, Digby
    Bass, Nicholas
    Crombie, Caroline
    Fraser, Gillian
    Kuan, Leh
    Walker, Nicholas
    McGhee, A
    Pickard, Ben
    Malloy, Pat
    Maclean, W
    Van Beck, Margaret
    Pato, T
    Medeiros, Helena
    Middleton, Frank
    Carvalho, Celia
    Morley, Christopher
    Fanous, Ayman
    Conti, David
    Knowles, A
    Ferreira, Paz
    Macedo, Antonio
    Azevedo, Helena
    Kirby, N
    Ferreira, R
    Daly, J
    Chambert, Kimberly
    Kuruvilla, Finny
    Gabriel, B
    Ardlie, Kristin
    Moran, Jennifer L.
    Common polygenic variation contributes to risk of schizophrenia and bipolar disorder2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 460, no 7256, 748-752 p.Article in journal (Refereed)
    Abstract [en]

    Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

  • 337. Pälike, Heiko
    et al.
    Lyle, Mitchell W.
    Nishi, Hiroshi
    Raffi, Isabella
    Ridgwell, Andy
    Gamage, Kusali
    Klaus, Adam
    Acton, Gary
    Anderson, Louise
    Backman, Jan
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Baldauf, Jack
    Beltran, Catherine
    Bohaty, Steven M.
    Bown, Paul
    Busch, William
    Channell, Jim E. T.
    Chun, Cecily O. J.
    Delaney, Margaret
    Dewangan, Pawan
    Jones, Tom Dunkley
    Edgar, Kirsty M.
    Evans, Helen
    Fitch, Peter
    Foster, Gavin L.
    Gussone, Nikolaus
    Hasegawa, Hitoshi
    Hathorne, Ed C.
    Hayashi, Hiroki
    Herrle, Jens O.
    Holbourn, Ann
    Hovan, Steve
    Hyeong, Kiseong
    Iijima, Koichi
    Ito, Takashi
    Kamikuri, Shin-ichi
    Kimoto, Katsunori
    Kuroda, Junichiro
    Leon-Rodriguez, Lizette
    Malinverno, Alberto
    Moore, Ted C., Jr.
    Murphy, Brandon H.
    Murphy, Daniel P.
    Nakamura, Hideto
    Ogane, Kaoru
    Ohneiser, Christian
    Richter, Carl
    Robinson, Rebecca
    Rohling, Eelco J.
    Romero, Oscar
    Sawada, Ken
    Scher, Howie
    Schneider, Leah
    Sluijs, Appy
    Takata, Hiroyuki
    Tian, Jun
    Tsujimoto, Akira
    Wade, Bridget S.
    Westerhold, Thomas
    Wilkens, Roy
    Williams, Trevor
    Wilson, Paul A.
    Yamamoto, Yuhji
    Yamamoto, Shinya
    Yamazaki, Toshitsugu
    Zeebe, Richard E.
    A Cenozoic record of the equatorial Pacific carbonate compensation depth2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 488, no 7413, 609-614 p.Article in journal (Refereed)
    Abstract [en]

    Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5 kilometres during the early Cenozoic (approximately 55 million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.

  • 338. Qiu, J
    Flight of the navigators2005In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 437, no 7060, 804-806 p.Article in journal (Refereed)
    Abstract [en]

    The Arctic is a unique testing ground for studying how birds navigate long distances, one of ornithology’s greatest mysteries. Birds use a number of different navigational cues, the Earth’s magnetic field, the landscape and the position of the Sun and stars. Studies on bird navigation will have implications forpreventing or containing animal based epidemics such as avian influenza.

  • 339.
    Qu, Qingming
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
    Haitina, Tatjana
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Zhu, Min
    Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences.
    Ahlberg, Per Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    New genomic and fossil data illuminate the origin of enamel2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 526, no 7571, 108-120 p.Article in journal (Refereed)
    Abstract [en]

    Enamel, the hardest vertebrate tissue, covers the teeth of almost all sarcopterygians (lobe-finned bony fishes and tetrapods) as well as the scales and dermal bones of many fossil lobe-fins(1-5). Enamel deposition requires an organic matrix containing the unique enamel matrix proteins (EMPs) amelogenin (AMEL), enamelin (ENAM) and ameloblastin (AMBN)(6). Chondrichthyans (cartilaginous fishes) lack both enamel and EMP genes(7,8). Many fossil and a few living non-teleost actinopterygians (ray-finned bony fishes) such as the gar, Lepisosteus, have scales and dermal bones covered with a proposed enamel homologue called ganoine(1,9). However, no gene or transcript data for EMPs have been described from actinopterygians(10,11). Here we show that Psarolepis romeri, a bony fish from the the Early Devonian period, combines enamel-covered dermal odontodes on scales and skull bones with teeth of naked dentine, and that Lepisosteus oculatus (the spotted gar) has enam andambn genes that are expressed in the skin, probably associated with ganoine formation. The genetic evidence strengthens the hypothesis that ganoine is homologous with enamel. The fossil evidence, further supported by the Silurian bony fish Andreolepis, which has enamel-covered scales but teeth and odontodes on its dermal bones made of naked dentine(12-16), indicates that this tissue originated on the dermal skeleton, probably on the scales. It subsequently underwent heterotopic expansion across two highly conserved patterning boundaries (scales/head-shoulder and dermal/oral) within the odontode skeleton.

  • 340. Raghavan, Maanasa
    et al.
    Skoglund, Pontus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Graf, Kelly E.
    Metspalu, Mait
    Albrechtsen, Anders
    Moltke, Ida
    Rasmussen, Simon
    Stafford, Thomas W., Jr.
    Orlando, Ludovic
    Metspalu, Ene
    Karmin, Monika
    Tambets, Kristiina
    Rootsi, Siiri
    Maegi, Reedik
    Campos, Paula F.
    Balanovska, Elena
    Balanovsky, Oleg
    Khusnutdinova, Elza
    Litvinov, Sergey
    Osipova, Ludmila P.
    Fedorova, Sardana A.
    Voevoda, Mikhail I.
    DeGiorgio, Michael
    Sicheritz-Ponten, Thomas
    Brunak, Soren
    Demeshchenko, Svetlana
    Kivisild, Toomas
    Villems, Richard
    Nielsen, Rasmus
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Willerslev, Eske
    Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 505, no 7481, 87-+ p.Article in journal (Refereed)
    Abstract [en]

    The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians(1-3), there is no consensus with regard to which specific Old World populations they are closest to(4-8). Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal'ta in south-central Siberia(9), to an average depth of 1x. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers(10-12), and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages(5). Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians(2,13). Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago(14), revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans.

  • 341. Rasmussen, Morten
    et al.
    Anzick, Sarah L.
    Waters, Michael R.
    Skoglund, Pontus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    DeGiorgio, Michael
    Stafford, Thomas W., Jr.
    Rasmussen, Simon
    Moltke, Ida
    Albrechtsen, Anders
    Doyle, Shane M.
    Poznik, G. David
    Gudmundsdottir, Valborg
    Yadav, Rachita
    Malaspinas, Anna-Sapfo
    White, Samuel Stockton
    Allentoft, Morten E.
    Cornejo, Omar E.
    Tambets, Kristiina
    Eriksson, Anders
    Heintzman, Peter D.
    Karmin, Monika
    Korneliussen, Thorfinn Sand
    Meltzer, David J.
    Pierre, Tracey L.
    Stenderup, Jesper
    Saag, Lauri
    Warmuth, Vera M.
    Lopes, Margarida C.
    Malhi, Ripan S.
    Brunak, Soren
    Sicheritz-Ponten, Thomas
    Barnes, Ian
    Collins, Matthew
    Orlando, Ludovic
    Balloux, Francois
    Manica, Andrea
    Gupta, Ramneek
    Metspalu, Mait
    Bustamante, Carlos D.
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nielsen, Rasmus
    Willerslev, Eske
    The genome of a Late Pleistocene human from a Clovis burial site in western Montana2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 506, no 7487, 225-229 p.Article in journal (Refereed)
    Abstract [en]

    Clovis, with its distinctive biface, blade and osseous technologies, is the oldest widespread archaeological complex defined in North America, dating from 11,100 to 10,700 C-14 years before present (BP) (13,000 to 12,600 calendar years BP)(1,2). Nearly 50 years of archaeological research point to the Clovis complex as having developed south of the North American ice sheets from an ancestral technology(3). However, both the origins and the genetic legacy of the people who manufactured Clovis tools remain under debate. It is generally believed that these people ultimately derived from Asia and were directly related to contemporary Native Americans(2). An alternative, Solutrean, hypothesis posits that the Clovis predecessors emigrated from southwestern Europe during the Last Glacial Maximum(4). Here we report the genome sequence of a male infant (Anzick-1) recovered from the Anzick burial site in western Montana. The human bones date to 10,705 +/- 35 C-14 years BP (approximately 12,707-12,556 calendar years BP) and were directly associated with Clovis tools. We sequenced the genome to an average depth of 14.4x and show that the gene flow from the Siberian Upper Palaeolithic Mal'ta population(5) into Native American ancestors is also shared by the Anzick-1 individual and thus happened before 12,600 years BP. We also show that the Anzick-1 individual is more closely related to all indigenous American populations than to any other group. Our data are compatible with the hypothesis that Anzick-1 belonged to a population directly ancestral to many contemporary Native Americans. Finally, we find evidence of a deep divergence in Native American populations that predates the Anzick-1 individual.

  • 342. Raymond, Peter A.
    et al.
    Hartmann, Jens
    Lauerwald, Ronny
    Sobek, Sebastian
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    McDonald, Cory
    Hoover, Mark
    Butman, David
    Striegl, Robert
    Mayorga, Emilio
    Humborg, Christoph
    Kortelainen, Pirkko
    Duerr, Hans
    Meybeck, Michel
    Ciais, Philippe
    Guth, Peter
    Global carbon dioxide emissions from inland waters2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 503, no 7476, 355-359 p.Article in journal (Refereed)
    Abstract [en]

    Carbon dioxide (CO2) transfer from inland waters to the atmosphere, known as CO2 evasion, is a component of the global carbon cycle. Global estimates of CO2 evasion have been hampered, however, by the lack of a framework for estimating the inland water surface area and gas transfer velocity and by the absence of a global CO2 database. Here we report regional variations in global inland water surface area, dissolved CO2 and gas transfer velocity. We obtain global CO2 evasion rates of 1.8(-0.25)(+0.25) petagrams of carbon (Pg C) per year from streams and rivers and 0.32(-0.26)(+0.52) Pg C yr(-1) from lakes and reservoirs, where the upper and lower limits are respectively the 5th and 95th confidence interval percentiles. The resulting global evasion rate of 2.1 Pg C yr(-1) is higher than previous estimates owing to a larger stream and river evasion rate. Our analysis predicts global hotspots in stream and river evasion, with about 70 per cent of the flux occurring over just 20 per cent of the land surface. The source of inland water CO2 is still not known with certainty and new studies are needed to research the mechanisms controlling CO2 evasion globally.

  • 343. Raymond, Peter A.
    et al.
    Hartmann, Jens
    Lauerwald, Ronny
    Sobek, Sebastian
    McDonald, Cory
    Hoover, Mark
    Butman, David
    Striegl, Robert
    Mayorga, Emilio
    Humborg, Christoph
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Kortelainen, Pirkko
    Duerr, Hans
    Meybeck, Michel
    Ciais, Philippe
    Guth, Peter
    Global carbon dioxide emissions from inland waters2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 503, no 7476, 355-359 p.Article in journal (Refereed)
    Abstract [en]

    Carbon dioxide (CO2) transfer from inland waters to the atmosphere, known as CO2 evasion, is a component of the global carbon cycle. Global estimates of CO2 evasion have been hampered, however, by the lack of a framework for estimating the inland water surface area and gas transfer velocity and by the absence of a global CO2 database. Here we report regional variations in global inland water surface area, dissolved CO2 and gas transfer velocity. We obtain global CO2 evasion rates of 1.8(-0.25)(+0.25) petagrams of carbon (Pg C) per year from streams and rivers and 0.32(-0.26)(+0.52) Pg C yr(-1) from lakes and reservoirs, where the upper and lower limits are respectively the 5th and 95th confidence interval percentiles. The resulting global evasion rate of 2.1 Pg C yr(-1) is higher than previous estimates owing to a larger stream and river evasion rate. Our analysis predicts global hotspots in stream and river evasion, with about 70 per cent of the flux occurring over just 20 per cent of the land surface. The source of inland water CO2 is still not known with certainty and new studies are needed to research the mechanisms controlling CO2 evasion globally.

  • 344. Reichstein, Markus
    et al.
    Bahn, Michael
    Ciais, Philippe
    Frank, Dorothea
    Mahecha, Miguel D.
    Seneviratne, Sonia I.
    Zscheischler, Jakob
    Beer, Christian
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Buchmann, Nina
    Frank, David C.
    Papale, Dario
    Rammig, Anja
    Smith, Pete
    Thonicke, Kirsten
    van der Velde, Marijn
    Vicca, Sara
    Walz, Ariane
    Wattenbach, Martin
    Climate extremes and the carbon cycle2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 500, no 7462, 287-295 p.Article in journal (Refereed)
    Abstract [en]

    The terrestrial biosphere is a key component of the global carbon cycle and its carbon balance is strongly influenced by climate. Continuing environmental changes are thought to increase global terrestrial carbon uptake. But evidence is mounting that climate extremes such as droughts or storms can lead to a decrease in regional ecosystem carbon stocks and therefore have the potential to negate an expected increase in terrestrial carbon uptake. Here we explore the mechanisms and impacts of climate extremes on the terrestrial carbon cycle, and propose a pathway to improve our understanding of present and future impacts of climate extremes on the terrestrial carbon budget.

  • 345. Reischauer, Sven
    et al.
    Stone, Oliver A.
    Villasenor, Alethia
    Chi, Neil
    Jin, Suk-Won
    Martin, Marcel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Lee, Miler T.
    Fukuda, Nana
    Marass, Michele
    Witty, Alec
    Fiddes, Ian
    Kuo, Taiyi
    Chung, Won-Suk
    Salek, Sherveen
    Lerrigo, Robert
    Alsio, Jessica
    Luo, Shujun
    Tworus, Dominika
    Augustine, Sruthy M.
    Mucenieks, Sophie
    Nystedt, Bjorn
    Giraldez, Antonio J.
    Schroth, Gary P.
    Andersson, Olov
    Stainier, Didier Y. R.
    Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 535, no 7611, 294-298 p.Article in journal (Refereed)
    Abstract [en]

    Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells(1-4) and a significant increase in cardiomyocyte numbers(5). Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation(1-7) and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location. Here we used a deletion allele of cloche to identify several new cloche candidate genes within this genomic region, and systematically genome-edited each candidate. Through this comprehensive interrogation, we succeeded in isolating the cloche gene and discovered that it encodes a PAS-domain-containing bHLH transcription factor, and that it is expressed in a highly specific spatiotemporal pattern starting during late gastrulation. Gain-of-function experiments show that it can potently induce endothelial gene expression. Epistasis experiments reveal that it functions upstream of etv2 and tal1, the earliest expressed endothelial and haematopoietic transcription factor genes identified to date. A mammalian cloche orthologue can also rescue blood vessel formation in zebrafish cloche mutants, indicating a highly conserved role in vertebrate vasculogenesis and haematopoiesis. The identification of this master regulator of endothelial and haematopoietic fate enhances our understanding of early mesoderm diversification and may lead to improved protocols for the generation of endothelial and haematopoietic cells in vivo and in vitro.

  • 346.
    Reischauer, Sven
    et al.
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany..
    Stone, Oliver A.
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany..
    Villasenor, Alethia
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany..
    Chi, Neil
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Univ Calif San Diego, Inst Genom Med, Div Cardiol, Dept Med, La Jolla, CA 92037 USA..
    Jin, Suk-Won
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Gwangju Inst Sci & Technol, Sch Life Sci, Gwangju 61005, South Korea.;Yale Univ, Sch Med, Yale Cardiovasc Res Ctr, New Haven, CT 06511 USA..
    Martin, Marcel
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-17121 Solna, Sweden..
    Lee, Miler T.
    Yale Univ, Dept Genet, Sch Med, New Haven, CT 06520 USA.;Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA..
    Fukuda, Nana
    Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany..
    Marass, Michele
    Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany..
    Witty, Alec
    Univ Calif San Diego, Inst Genom Med, Div Cardiol, Dept Med, La Jolla, CA 92037 USA..
    Fiddes, Ian
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Univ Calif Santa Cruz, Genom Inst, Santa Cruz, CA 95064 USA.;Howard Hughes Med Inst, Santa Cruz, CA 95064 USA..
    Kuo, Taiyi
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA.;Columbia Univ Coll Phys & Surg, Berrie Diabet Ctr, 630 W 168th St, New York, NY 10032 USA..
    Chung, Won-Suk
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon 34141, South Korea..
    Salek, Sherveen
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21224 USA..
    Lerrigo, Robert
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Univ Washington, Div Gen Internal Med, Seattle, WA 98104 USA..
    Alsio, Jessica
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Novartis, CH-4056 Basel, Switzerland..
    Luo, Shujun
    Illumina, San Diego, CA 92122 USA.;Personalis, Menlo Pk, CA 94025 USA..
    Tworus, Dominika
    Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden..
    Augustine, Sruthy M.
    Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany..
    Mucenieks, Sophie
    Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany..
    Nystedt, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Giraldez, Antonio J.
    Yale Univ, Dept Genet, Sch Med, New Haven, CT 06520 USA..
    Schroth, Gary P.
    Illumina, San Diego, CA 92122 USA..
    Andersson, Olov
    Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden..
    Stainier, Didier Y. R.
    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany..
    Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 535, no 7611, 294-+ p.Article in journal (Refereed)
    Abstract [en]

    Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells(1-4) and a significant increase in cardiomyocyte numbers(5). Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation(1-7) and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location. Here we used a deletion allele of cloche to identify several new cloche candidate genes within this genomic region, and systematically genome-edited each candidate. Through this comprehensive interrogation, we succeeded in isolating the cloche gene and discovered that it encodes a PAS-domain-containing bHLH transcription factor, and that it is expressed in a highly specific spatiotemporal pattern starting during late gastrulation. Gain-of-function experiments show that it can potently induce endothelial gene expression. Epistasis experiments reveal that it functions upstream of etv2 and tal1, the earliest expressed endothelial and haematopoietic transcription factor genes identified to date. A mammalian cloche orthologue can also rescue blood vessel formation in zebrafish cloche mutants, indicating a highly conserved role in vertebrate vasculogenesis and haematopoiesis. The identification of this master regulator of endothelial and haematopoietic fate enhances our understanding of early mesoderm diversification and may lead to improved protocols for the generation of endothelial and haematopoietic cells in vivo and in vitro.

  • 347.
    Reuveni, Shlomi
    et al.
    Harvard Univ, Dept Syst Biol, HMS, 200 Longwood Ave, Boston, MA 02115 USA..
    Ehrenberg, Måns
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Paulsson, Johan
    Harvard Univ, Dept Syst Biol, HMS, 200 Longwood Ave, Boston, MA 02115 USA..
    Ribosomes are optimized for autocatalytic production2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 547, no 7663, 293-297 p.Article in journal (Refereed)
    Abstract [en]

    Many fine-scale features of ribosomes have been explained in terms of function, revealing a molecular machine that is optimized for error-correction, speed and control. Here we demonstrate mathematically that many less well understood, larger-scale features of ribosomes-such as why a few ribosomal RNA molecules dominate the mass and why the ribosomal protein content is divided into 55-80 small, similarly sized segments-speed up their autocatalytic production.

  • 348.
    Ribbing, Carl-Gustaf
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Longitude Prize now an objective decision2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 511, no 7507, 31-31 p.Article in journal (Refereed)
  • 349. Ripke, Stephan
    et al.
    Neale, Benjamin M.
    Corvin, Aiden
    Walters, James T. R.
    Farh, Kai-How
    Holmans, Peter A.
    Lee, Phil
    Bulik-Sullivan, Brendan
    Collier, David A.
    Huang, Hailiang
    Pers, Tune H.
    Agartz, Ingrid
    Agerbo, Esben
    Albus, Margot
    Alexander, Madeline
    Amin, Farooq
    Bacanu, Silviu A.
    Begemann, Martin
    Belliveau, Richard A., Jr.
    Bene, Judit
    Bergen, Sarah E.
    Bevilacqua, Elizabeth
    Bigdeli, Tim B.
    Black, Donald W.
    Bruggeman, Richard
    Buccola, Nancy G.
    Buckner, Randy L.
    Byerley, William
    Cahn, Wiepke
    Cai, Guiqing
    Campion, Dominique
    Cantor, Rita M.
    Carr, Vaughan J.
    Carrera, Noa
    Catts, Stanley V.
    Chambert, Kimberly D.
    Chan, Raymond C. K.
    Chen, Ronald Y. L.
    Chen, Eric Y. H.
    Cheng, Wei
    Cheung, Eric F. C.
    Chong, Siow Ann
    Cloninger, C. Robert
    Cohen, David
    Cohen, Nadine
    Cormican, Paul
    Craddock, Nick
    Crowley, James J.
    Curtis, David
    Davidson, Michael
    Davis, Kenneth L.
    Degenhardt, Franziska
    Del Favero, Jurgen
    Demontis, Ditte
    Dikeos, Dimitris
    Dinan, Timothy
    Djurovic, Srdjan
    Donohoe, Gary
    Drapeau, Elodie
    Duan, Jubao
    Dudbridge, Frank
    Durmishi, Naser
    Eichhammer, Peter
    Eriksson, Johan
    Escott-Price, Valentina
    Essioux, Laurent
    Fanous, Ayman H.
    Farrell, Martilias S.
    Frank, Josef
    Franke, Lude
    Freedman, Robert
    Freimer, Nelson B.
    Friedl, Marion
    Friedman, Joseph I.
    Fromer, Menachem
    Genovese, Giulio
    Georgieva, Lyudmila
    Giegling, Ina
    Giusti-Rodriguez, Paola
    Godard, Stephanie
    Goldstein, Jacqueline I.
    Golimbet, Vera
    Gopal, Srihari
    Gratten, Jacob
    de Haan, Lieuwe
    Hammer, Christian
    Hamshere, Marian L.
    Hansen, Mark
    Hansen, Thomas
    Haroutunian, Vahram
    Hartmann, Annette M.
    Henskens, Frans A.
    Herms, Stefan
    Hirschhorn, Joel N.
    Hoffmann, Per
    Hofman, Andrea
    Hollegaard, Mads V.
    Hougaard, David M.
    Ikeda, Masashi
    Joa, Inge
    Julia, Antonio
    Kahn, Rene S.
    Kalaydjieva, Luba
    Karachanak-Yankova, Sena
    Karjalainen, Juha
    Kavanagh, David
    Keller, Matthew C.
    Kennedy, James L.
    Khrunin, Andrey
    Kim, Yunjung
    Klovins, Janis
    Knowles, James A.
    Konte, Bettina
    Kucinskas, Vaidutis
    Kucinskiene, Zita Ausrele
    Kuzelova-Ptackova, Hana
    Kahler, Anna K.
    Laurent, Claudine
    Keong, Jimmy Lee Chee
    Lee, S. Hong
    Legge, Sophie E.
    Lerer, Bernard
    Li, Miaoxin
    Li, Tao
    Liang, Kung-Yee
    Lieberman, Jeffrey
    Limborska, Svetlana
    Loughland, Carmel M.
    Lubinski, Jan
    Lonnqvist, Jouko
    Macek, Milan, Jr.
    Magnusson, Patrik K. E.
    Maher, Brion S.
    Maier, Wolfgang
    Mallet, Jacques
    Marsal, Sara
    Mattheisen, Manuel
    Mattingsdal, Morten
    McCarley, Robert W.
    McDonald, Colm
    McIntosh, Andrew M.
    Meier, Sandra
    Meijer, Carin J.
    Melegh, Bela
    Melle, Ingrid
    Mesholam-Gately, Raquelle I.
    Metspalu, Andres
    Michie, Patricia T.
    Milani, Lili
    Milanova, Vihra
    Mokrab, Younes
    Morris, Derek W.
    Mors, Ole
    Murphy, Kieran C.
    Murray, Robin M.
    Myin-Germeys, Inez
    Mueller-Myhsok, Bertram
    Nelis, Mari
    Nenadic, Igor
    Nertney, Deborah A.
    Nestadt, Gerald
    Nicodemus, Kristin K.
    Nikitina-Zake, Liene
    Nisenbaum, Laura
    Nordin, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    O'Callaghan, Eadbhard
    O'Dushlaine, Colm
    O'Neill, F. Anthony
    Oh, Sang-Yun
    Olincy, Ann
    Olsen, Line
    Van Os, Jim
    Pantelis, Christos
    Papadimitriou, George N.
    Papiol, Sergi
    Parkhomenko, Elena
    Pato, Michele T.
    Paunio, Tiina
    Pejovic-Milovancevic, Milica
    Perkins, Diana O.
    Pietilainen, Olli
    Pimm, Jonathan
    Pocklington, Andrew J.
    Powell, John
    Price, Alkes
    Pulver, Ann E.
    Purcell, Shaun M.
    Quested, Digby
    Rasmussen, Henrik B.
    Reichenberg, Abraham
    Reimers, Mark A.
    Richards, Alexander L.
    Roffman, Joshua L.
    Roussos, Panos
    Ruderfer, Douglas M.
    Salomaa, Veikko
    Sanders, Alan R.
    Schall, Ulrich
    Schubert, Christian R.
    Schulze, Thomas G.
    Schwab, Sibylle G.
    Scolnick, Edward M.
    Scott, Rodney J.
    Seidman, Larry J.
    Shi, Jianxin
    Sigurdsson, Engilbert
    Silagadze, Teimuraz
    Silverman, Jeremy M.
    Sim, Kang
    Slominsky, Petr
    Smoller, Jordan W.
    So, Hon-Cheong
    Spencer, Chris C. A.
    Stahl, Eli A.
    Stefansson, Hreinn
    Steinberg, Stacy
    Stogmann, Elisabeth
    Straub, Richard E.
    Strengman, Eric
    Strohmaier, Jana
    Stroup, T. Scott
    Subramaniam, Mythily
    Suvisaari, Jaana
    Svrakic, Dragan M.
    Szatkiewicz, Jin P.
    Soderman, Erik
    Thirumalai, Srinivas
    Toncheva, Draga
    Tosato, Sarah
    Veijola, Juha
    Waddington, John
    Walsh, Dermot
    Wang, Dai
    Wang, Qiang
    Webb, Bradley T.
    Weiser, Mark
    Wildenauer, Dieter B.
    Williams, Nigel M.
    Williams, Stephanie
    Witt, Stephanie H.
    Wolen, Aaron R.
    Wong, Emily H. M.
    Wormley, Brandon K.
    Xi, Hualin Simon
    Zai, Clement C.
    Zheng, Xuebin
    Zimprich, Fritz
    Wray, Naomi R.
    Stefansson, Kari
    Visscher, Peter M.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Andreassen, Ole A.
    Blackwood, Douglas H. R.
    Bramon, Elvira
    Buxbaum, Joseph D.
    Borglum, Anders D.
    Cichon, Sven
    Darvasi, Ariel
    Domenici, Enrico
    Ehrenreich, Hannelore
    Esko, Tonu
    Gejman, Pablo V.
    Gill, Michael
    Gurling, Hugh
    Hultman, Christina M.
    Iwata, Nakao
    Jablensky, Assen V.
    Jonsson, Erik G.
    Kendler, Kenneth S.
    Kirov, George
    Knight, Jo
    Lencz, Todd
    Levinson, Douglas F.
    Li, Qingqin S.
    Liu, Jianjun
    Malhotra, Anil K.
    McCarroll, Steven A.
    McQuillin, Andrew
    Moran, Jennifer L.
    Mortensen, Preben B.
    Mowry, Bryan J.
    Noethen, Markus M.
    Ophoff, Roel A.
    Owen, Michael J.
    Palotie, Aarno
    Pato, Carlos N.
    Petryshen, Tracey L.
    Posthuma, Danielle
    Rietschel, Marcella
    Riley, Brien P.
    Rujescu, Dan
    Sham, Pak C.
    Sklar, Pamela
    St Clair, David
    Weinberger, Daniel R.
    Wendland, Jens R.
    Werge, Thomas
    Daly, Mark J.
    Sullivan, Patrick F.
    O'Donovan, Michael C.
    Biological insights from 108 schizophrenia-associated genetic loci2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 511, no 7510, 421-427 p.Article in journal (Refereed)
    Abstract [en]

    Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

  • 350.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Misconceptions of global catastrophe2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 532, no 7599, 317-318 p.Article in journal (Other academic)
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