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Analysis of heritability and shared heritability based on Genome-Wide Association Studies for 13 Cancer Types
- Publication Year :
- 2015
- Publisher :
- Oxford University Press, 2015.
-
Abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common SNPs for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49,492 cancer cases and 34,131 controls. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% CI = 14% - 37%) and 7% (4% - 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ=0.73, SE=0.28), Diffuse Large B-Cell Lymphoma (DLBCL) and pediatric osteosarcoma (ρ=0.53, SE=0.21), DLBCL and Chronic Lymphocytic Leukemia (CLL) (ρ=0.51, SE=0.18), and bladder and lung (ρ=0.35, SE=0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a non-smoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
- Subjects :
- Adult
Asian Continental Ancestry Group
Male
Lung Neoplasms
DATABASE
European Continental Ancestry Group
RELATIVES
Bone Neoplasms
Polymorphism, Single Nucleotide
Article
LUNG-CANCER
Testicular Neoplasms
Neoplasms
SWEDEN
LYMPHOMA
Humans
Genetic Predisposition to Disease
FAMILIAL RISK
Oncology & Carcinogenesis
Aged
Osteosarcoma
Science & Technology
MUTATIONS
Smoking
Middle Aged
Leukemia, Lymphocytic, Chronic, B-Cell
PANCREATIC-CANCER
Kidney Neoplasms
MULTIPLE SUSCEPTIBILITY LOCI
INDIVIDUALS
Oncology
Urinary Bladder Neoplasms
Tissue Array Analysis
Female
Lymphoma, Large B-Cell, Diffuse
Life Sciences & Biomedicine
1112 Oncology And Carcinogenesis
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.pmid.dedup....f4c7d41142bfb127c07c4f9d447a5d47