Shared heritability and functional enrichment across six solid cancers

Jiang, Xia; Kogevinas, Manolis; Koutros, Stella; Lindström, Sara

doi:http://dx.doi.org/10.1038/s41467-018-08054-4

Shared heritability and functional enrichment across six solid cancers

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Jiang X, Finucane HK, Schumacher FR, Schmit SL, Tyrer JP, Han Y. et al. Shared heritability and functional enrichment across six solid cancers. Nat Commun. 2019 Jan 25;10(1):431.DOI: 10.1038/s41467-018-08054-4

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.