Bayesian variable selection with a pleiotropic loss function in Mendelian randomization. (21st June 2021) - Gkatzionis, Apostolos
Abstract : Mendelian randomization is the use of genetic variants as instruments to assess the existence of a causal relationship between a risk factor and an outcome. A Mendelian randomization analysis requires a set of genetic variants that are strongly associated with the risk factor and only associated with the outcome through their effect on the risk factor. We describe a novel variable selection algorithm for Mendelian randomization that can identify sets of genetic variants which are suitable in both these respects. Our algorithm is applicable in the context of two‐sample summary‐data Mendelian randomization and employs a recently proposed theoretical extension of the traditional Bayesian statistics framework, including a loss function to penalize genetic variants that exhibit pleiotropic effects. The algorithm offers robust inference through the use of model averaging, as we illustrate by running it on a range of simulation scenarios and comparing it against established pleiotropy‐robust Mendelian randomization methods. In a real‐data application, we study the effect of systolic and diastolic blood pressure on the risk of suffering from coronary heart disease (CHD). Based on a recent large‐scale GWAS for blood pressure, we use 395 genetic variants for systolic and 391 variants for diastolic blood pressure. Both traits are shown to have significant risk‐increasing effects on CHD risk.