Adjusting for covariates in variance components QTL linkage analysis

Variance components modeling has emerged as a powerful method for quantitative trait loci (QTL) linkage analysis. However, the power to detect a gene of minor effect is low. Many complex traits are affected by environmental as well as genetic factors, and one strategy to increase power is to reduce nongenetic phenotypic variance by adjusting for environmental covariates. In this paper, we investigate the power of three approaches to covariate adjustment in variance components linkage analysis: (i) incorporate covariates in the means model, (ii) incorporate covariates in the covariance matrix, and (iii) perform analysis on residual statistics. These approaches are compared to an analysis without adjustment. The results show that in the absence of correlation between the covariate and the QTL effect, adjusting for covariates indeed increases power to detect an underlying QTL. As this correlation increases, however, the power decreases. In the presence of a causal association between QTL and covariates, not adjusting for covariates appeared to be more powerful. The three approaches for adjusting for covariate: residual statistics, the means model, and the covariance model, had equal power to detect a QTL.