Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome

Abstract

Background: Sample size calculations are an important tool for planning epidemiological studies. Large sample sizes are often required in Mendelian randomization investigations.Methods and results: Resources are provided for investigators to perform sample size and power calculations for Mendelian randomization with a binary outcome. We initially provide formulae for the continuous outcome case, and then analogous formulae for the binary outcome case. The formulae are valid for a single instrumental variable, which may be a single genetic variant or an allele score comprising multiple variants. Graphs are provided to give the required sample size for 80% power for given values of the causal effect of the risk factor on the outcome and of the squared correlation between the risk factor and instrumental variable. R code and an online calculator tool are made available for calculating the sample size needed for a chosen power level given these parameters, as well as the power given the chosen sample size and these parameters.Conclusions: The sample size required for a given power of Mendelian randomization investigation depends greatly on the proportion of variance in the risk factor explained by the instrumental variable. The inclusion of multiple variants into an allele score to explain more of the variance in the risk factor will improve power, however care must be taken not to introduce bias by the inclusion of invalid variants.