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Distribution of allele frequencies and effect sizes and their interrelationships for common genetic susceptibility variants.

ABSTRACT: Recent discoveries of hundreds of common susceptibility SNPs from genome-wide association studies provide a unique opportunity to examine population genetic models for complex traits. In this report, we investigate distributions of various population genetic parameters and their interrelationships using estimates of allele frequencies and effect-size parameters for about 400 susceptibility SNPs across a spectrum of qualitative and quantitative traits. We calibrate our analysis by statistical power for detection of SNPs to account for overrepresentation of variants with larger effect sizes in currently known SNPs that are expected due to statistical power for discovery. Across all qualitative disease traits, minor alleles conferred "risk" more often than "protection." Across all traits, an inverse relationship existed between "regression effects" and allele frequencies. Both of these trends were remarkably strong for type I diabetes, a trait that is most likely to be influenced by selection, but were modest for other traits such as human height or late-onset diseases such as type II diabetes and cancers. Across all traits, the estimated effect-size distribution suggested the existence of increasingly large numbers of susceptibility SNPs with decreasingly small effects. For most traits, the set of SNPs with intermediate minor allele frequencies (5-20%) contained an unusually small number of susceptibility loci and explained a relatively small fraction of heritability compared with what would be expected from the distribution of SNPs in the general population. These trends could have several implications for future studies of common and uncommon variants.

SUBMITTER: Park JH

PROVIDER: S-EPMC3207674 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Distribution of allele frequencies and effect sizes and their interrelationships for common genetic susceptibility variants.

Park Ju-Hyun JH Gail Mitchell H MH Weinberg Clarice R CR Carroll Raymond J RJ Chung Charles C CC Wang Zhaoming Z Chanock Stephen J SJ Fraumeni Joseph F JF Chatterjee Nilanjan N

Proceedings of the National Academy of Sciences of the United States of America 20111014 44

Recent discoveries of hundreds of common susceptibility SNPs from genome-wide association studies provide a unique opportunity to examine population genetic models for complex traits. In this report, we investigate distributions of various population genetic parameters and their interrelationships using estimates of allele frequencies and effect-size parameters for about 400 susceptibility SNPs across a spectrum of qualitative and quantitative traits. We calibrate our analysis by statistical pow ...[more]

PMID: 22003128

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Distribution of allele frequencies and effect sizes and their interrelationships for common genetic susceptibility variants.

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Distribution of allele frequencies and effect sizes and their interrelationships for common genetic susceptibility variants.

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