Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-18246-6
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Funding
- National Institutes of Health [R01CA088164, R01CA201358, R25CA112355, K07CA188142, K24CA169004, U01CA127298]
- UCSF Goldberg-Benioff Program in Cancer Translational Biology
- National Institute on Aging
- NIH Common Fund [RC2 AG036607]
- National Institute of Mental Health
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Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility. Pleiotropic loci and genome-wide genetic correlations have identified shared heritability across some types of cancers. Here, the authors perform genome-wide association studies and characterize pan-cancer heritability and pleiotropy in individuals of European ancestry across 18 cancer types from two large cohorts.
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