Re-ranking sequencing variants in the post-GWAS era for accurate causal variant identification.

ABSTRACT: Next generation sequencing has dramatically increased our ability to localize disease-causing variants by providing base-pair level information at costs increasingly feasible for the large sample sizes required to detect complex-trait associations. Yet, identification of causal variants within an established region of association remains a challenge. Counter-intuitively, certain factors that increase power to detect an associated region can decrease power to localize the causal variant. First, combining GWAS with imputation or low coverage sequencing to achieve the large sample sizes required for high power can have the unintended effect of producing differential genotyping error among SNPs. This tends to bias the relative evidence for association toward better genotyped SNPs. Second, re-u

SUBMITTER: Faye LL 

PROVIDER: S-EPMC3738448 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature