- Main
Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
- Author(s): 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
- et al.
Published Web Location
https://doi.org/10.1038/s41467-020-18246-6Abstract
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.
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.