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Shared heritability and functional enrichment across six solid cancers
Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 677 Huntington Ave, Boston, MA 02115 USA;Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Nobels Vagen 13, S-17177 Stockholm, Sweden.
Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA;Broad Inst MIT & Harvard, Program Med & Populat Genet, 75 Ames St, Cambridge, MA 02142 USA.
Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, 10900 Eucid Ave, Cleveland, OH 44106 USA;Univ Hosp, Seidman Canc Ctr, Cleveland, OH 44106 USA.
H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, 12902 Magnolia Dr MRC CANCONT, Tampa, FL 33612 USA;H Lee Moffitt Canc Ctr & Res Inst, Dept Gastrointestinal Oncol, 12902 Magnolia Dr MRC CANCONT, Tampa, FL 33612 USA.
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2019 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 431Article in journal (Refereed) Published
Abstract [en]

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

Place, publisher, year, edition, pages
2019. Vol. 10, article id 431
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Medical Genetics
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URN: urn:nbn:se:uu:diva-377352DOI: 10.1038/s41467-018-08054-4ISI: 000456696700007PubMedID: 30683880OAI: oai:DiVA.org:uu-377352DiVA, id: diva2:1291062
Note

Correction in: NATURE COMMUNICATIONS, Volume: 10, Article Number: 4386, DOI: 10.1038/s41467-019-12095-8

Available from: 2019-02-22 Created: 2019-02-22 Last updated: 2019-10-11Bibliographically approved

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