Pan-Cancer Study Detects Novel Genetic Risk Variants and Shared Genetic Basis in Two Large Cohorts
| Autor: | Lawrence H. Kushi, Stephen K. Van Den Eeden, Eric Jorgenson, John S. Witte, Laurel A. Habel, Taylor B. Cavazos, Joshua D. Hoffman, Travis J. Meyers, Lori C. Sakoda, Rebecca E. Graff, Nima C. Emami, Stacey E. Alexeeff, Elad Ziv, Thomas J. Hoffmann, Sara R. Rashkin, Maruta A. Blatchins, Khanh K. Thai, Linda Kachuri, Douglas A. Corley |
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| Rok vydání: | 2019 |
| Předmět: |
Genetics
0303 health sciences education.field_of_study Population Cancer Genome-wide association study Heritability Biology medicine.disease Genetic architecture 3. Good health 03 medical and health sciences 0302 clinical medicine Genetic epidemiology Pleiotropy 030220 oncology & carcinogenesis medicine education 030304 developmental biology Genetic association |
| Popis: | Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. However, no studies have investigated pan-cancer pleiotropy within single, well-defined populations unselected for phenotype. We undertook novel 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 (413,870 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 detected 21 novel genome-wide significant risk variants. In addition, numerous cancer sites exhibited clear heritability. Investigations of pleiotropy identified 12 cancer pairs exhibiting either positive or negative genetic correlations and 43 pleiotropic loci. We identified 158 pleiotropic variants, many of which were enriched for regulatory elements and influenced cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility. |
| Databáze: | OpenAIRE |
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