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Shared heritability and functional enrichment across six solid cancers

Shared heritability and functional enrichment across six solid cancers

Title: Shared heritability and functional enrichment across six solid cancers
Author: Jiang, Xia
Finucane, Hilary K.
Schumacher, Fredrick R.
Schmit, Stephanie L.
Tyrer, Jonathan P.
Han, Younghun
Michailidou, Kyriaki
Lesseur, Corina
Kuchenbaecker, Karoline B.
Dennis, Joe
... 323 more authors Show all authors
Date: 2019-01-25
Language: English
Scope: 431
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Lífvísindasetur (HÍ)
Biomedical Center (UI)
Series: Nature Communications;10(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-018-08054-4
Subject: Cancer; Cancer genetics; Epidemiology; Genomics; Brjóstakrabbamein; Krabbamein; Erfðafræði; Erfðarannsóknir; Faraldsfræði
URI: https://hdl.handle.net/20.500.11815/1587

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Jiang, X., Finucane, H.K., Schumacher, F.R. et al. Shared heritability and functional enrichment across six solid cancers. Nat Commun 10, 431 (2019). https://doi.org/10.1038/s41467-018-08054-4


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 (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 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.


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