Bias in two-sample Mendelian randomization when using heritable covariable-adjusted summary associations.

ABSTRACT:

Background

Two-sample Mendelian randomization (MR) allows the use of freely accessible summary association results from genome-wide association studies (GWAS) to estimate causal effects of modifiable exposures on outcomes. Some GWAS adjust for heritable covariables in an attempt to estimate direct effects of genetic variants on the trait of interest. One, both or neither of the exposure GWAS and outcome GWAS may have been adjusted for covariables.

Methods

We performed a simulation study comprising different scenarios that could motivate covariable adjustment in a GWAS and analysed real data to assess the influence of using covariable-adjusted summary association results in two-sample MR.

Results

In the absence of residual confounding between exposure and covariable, b

SUBMITTER: Hartwig FP 

PROVIDER: S-EPMC8580279 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature