Avoiding bias from weak instruments in Mendelian randomization studies

Mendelian randomization is used to test and estimate the magnitude of a causal effect of a phenotype on an outcome by using genetic variants as instrumental variables (IVs). Estimates of association from IV analysis are biased in the direction of the confounded, observational association between phenotype and outcome. The magnitude of the bias depends on the F-statistic for the strength of relationship between IVs and phenotype. We seek to develop guidelines for the design and analysis of Mendelian randomization studies to minimize bias.

IV analysis was performed on simulated and real data to investigate the effect on bias of size of study, number and choice of instruments and method of analysis.