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Novel genetic loci associated with hippocampal volume
Univ Southern Calif, Imaging Genet Ctr, USC Mark & Mary Stevens Neuroimaging & Informat I, Keck Sch Med, Marina Del Rey, CA 90292 USA..
Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 CE Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, NL-3015 CE Rotterdam, Netherlands..
Univ Southern Calif, Imaging Genet Ctr, USC Mark & Mary Stevens Neuroimaging & Informat I, Keck Sch Med, Marina Del Rey, CA 90292 USA..
Univ Bordeaux, INSERM Unit U1219, F-33076 Bordeaux, France..
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 13624Article in journal (Refereed) Published
Abstract [en]

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Place, publisher, year, edition, pages
2017. Vol. 8, article id 13624
National Category
Medical Genetics
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URN: urn:nbn:se:uu:diva-316027DOI: 10.1038/ncomms13624ISI: 000392154900001PubMedID: 28098162OAI: oai:DiVA.org:uu-316027DiVA, id: diva2:1077232
Available from: 2017-02-27 Created: 2017-02-27 Last updated: 2018-01-13Bibliographically approved

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