A Comparison of Approaches to Control for Confounding Factors by Regression Models

Publisher: Karger

E-ISSN: 1423-0062|72|3|194-205

ISSN: 0001-5652

Source: Human Heredity, Vol.72, Iss.3, 2011-11, pp. : 194-205

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

A common technique to control for confounding factors in practice is by regression adjustment. There are various versions of regression modeling in the literature, and in this paper we considered four approaches often seen in genetic association studies. We carried out both analytical and simulation studies comparing the bias of effect size estimates and examining the test sizes under the null hypothesis of no association between an outcome and an exposure. Further, we compared the methods in a nonsynonymous genome-wide scan for plasma lipoprotein(a) levels using a dataset from the Dallas Heart Study. We found that a widely employed approach that models the covariate-adjusted outcome and the exposure leads to an infranominal test size and underestimation of the exposure effect size. In conclusion, we recommend either using multiple regression models or modeling the covariate-adjusted outcome and the covariate-adjusted exposure to control for confounding factors.