• Shared heritability and functional enrichment across six solid cancers

      Jiang, X; Finucane, H; Schumacher, F; Schmit, S; Tyrer, J; Han, Y; Michailidou, K; Lesseur, C; Kuchenbaecker, K; Dennis, J; et al. (2019)
      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.