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Title: A latent mixture model for heterogeneous causal mechanisms in mendelian randomization Authors:  Daniel Iong - University of Michigan, Ann Arbor (United States) [presenting]
Qingyuan Zhao - University of Cambridge (United Kingdom)
Yang Chen - University of Michigan (United States)
Abstract: Mendelian Randomization (MR) is a popular method in epidemiology and genetics that uses genetic variation as instrumental variables for causal inference. Existing MR methods usually assume most genetic variants are valid instrumental variables that identify a common causal effect. There is a general lack of awareness that this effect homogeneity assumption can be violated when there are multiple causal pathways involved, even if all the instrumental variables are valid. We introduce a latent mixture model MR-PATH that groups instruments that yield similar causal effect estimates together. We develop a Monte-Carlo EM algorithm to fit this mixture model, derive approximate confidence intervals for uncertainty quantification, and adopt a modified Bayesian Information Criterion (BIC) for model selection. We verify the efficacy of the Monte-Carlo EM algorithm, confidence intervals, and model selection criterion using numerical simulations. We identify potential mechanistic heterogeneity when applying our method to estimate the effect of high-density lipoprotein cholesterol on coronary heart disease and the effect of adiposity on type II diabetes.