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Shared heritability and functional enrichment across six solid cancers.

Published on Jan 25, 2019in Nature Communications11.88
· DOI :10.1038/s41467-018-08054-4
Xia Jiang5
Estimated H-index: 5
(KI: Karolinska Institutet),
Hilary K. Finucane24
Estimated H-index: 24
(Broad Institute)
+ 330 AuthorsSara Lindstroem43
Estimated H-index: 43
(UW: University of Washington)
Abstract
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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References63
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#1Sara Lindstroem (UW: University of Washington)H-Index: 43
#2Hilary K. Finucane (MIT: Massachusetts Institute of Technology)H-Index: 24
Last.Jennifer B. Permuth (USF: University of South Florida)H-Index: 6
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#1James D. McKay (IARC: International Agency for Research on Cancer)H-Index: 50
#2Rayjean J. Hung (U of T: University of Toronto)H-Index: 45
Last.Yafang Li (Dartmouth College)H-Index: 10
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Cited By6
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#1Hongjie Chen (UW: University of Washington)
#2Gleb Kichaev (UCLA: University of California, Los Angeles)H-Index: 12
Last.Sara Lindstroem (UW: University of Washington)H-Index: 43
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#1Zhishan Chen (Vandy: Vanderbilt University)
#2Wanqing Wen (Vandy: Vanderbilt University)H-Index: 51
Last.Qiuyin Cai (Vandy: Vanderbilt University)H-Index: 64
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#1Sara R. Rashkin (UCSF: University of California, San Francisco)H-Index: 1
#2Rebecca E. Graff (UCSF: University of California, San Francisco)H-Index: 11
Last.Joshua D. Hoffman (UCSF: University of California, San Francisco)H-Index: 8
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#1Linda Kachuri (UCSF: University of California, San Francisco)H-Index: 8
#2Mattias Johansson (IARC: International Agency for Research on Cancer)H-Index: 40
Last.Paolo Vineis (Imperial College London)H-Index: 110
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