Shared heritability and functional enrichment across six solid cancers

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<jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub> = 0.57, <jats:italic>p</jats:italic> = 4.6 × 10<jats:sup>−8</jats:sup>), breast and ovarian cancer (<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub> = 0.24, <jats:italic>p</jats:italic> = 7 × 10<jats:sup>−5</jats:sup>), breast and lung cancer (<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub> = 0.18, <jats:italic>p </jats:italic>=1.5 × 10<jats:sup>−6</jats:sup>) and breast and colorectal cancer (<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub> = 0.15, <jats:italic>p</jats:italic> = 1.1 × 10<jats:sup>−4</jats:sup>). 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.</jats:p>

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