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- Title
Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
- Authors
Rashkin, Sara R.; Graff, Rebecca E.; Kachuri, Linda; Thai, Khanh K.; Alexeeff, Stacey E.; Blatchins, Maruta A.; Cavazos, Taylor B.; Corley, Douglas A.; Emami, Nima C.; Hoffman, Joshua D.; Jorgenson, Eric; Kushi, Lawrence H.; Meyers, Travis J.; Van Den Eeden, Stephen K.; Ziv, Elad; Habel, Laurel A.; Hoffmann, Thomas J.; Sakoda, Lori C.; Witte, John S.
- Abstract
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.
- Subjects
UNITED Kingdom; GENETIC epidemiology; RISK sharing; GENETIC correlations; GENE expression; EPIDEMIOLOGICAL research; CIS-regulatory elements (Genetics); HERITABILITY
- Publication
Nature Communications, 2020, Vol 11, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-18246-6