Adjusting for heritable covariates can bias effect estimates in genome-wide association studies.

ABSTRACT: In recent years, a number of large-scale genome-wide association studies have been published for human traits adjusted for other correlated traits with a genetic basis. In most studies, the motivation for such an adjustment is to discover genetic variants associated with the primary outcome independently of the correlated trait. In this report, we contend that this objective is fulfilled when the tested variants have no effect on the covariate or when the correlation between the covariate and the outcome is fully explained by a direct effect of the covariate on the outcome. For all other scenarios, an unintended bias is introduced with respect to the primary outcome as a result of the adjustment, and this bias might lead to false positives. Here, we illustrate this point by providing examp

SUBMITTER: Aschard H 

PROVIDER: S-EPMC4320269 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature