Estimating genetic effects and quantifying missing heritability explained by identified rare-variant associations.

ABSTRACT: Next-generation sequencing has led to many complex-trait rare-variant (RV) association studies. Although single-variant association analysis can be performed, it is grossly underpowered. Therefore, researchers have developed many RV association tests that aggregate multiple variant sites across a genetic region (e.g., gene), and test for the association between the trait and the aggregated genotype. After these aggregate tests detect an association, it is only possible to estimate the average genetic effect for a group of RVs. As a result of the "winner's curse," such an estimate can be biased. Although for common variants one can obtain unbiased estimates of genetic parameters by analyzing a replication sample, for RVs it is desirable to obtain unbiased genetic estimates for the study whe

SUBMITTER: Liu DJ 

PROVIDER: S-EPMC3484659 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature