Inferring the Direction of a Causal Link and Estimating Its Effect via a Bayesian Mendelian Randomization Approach

TL;DR

This paper introduces BayesMR, a Bayesian Mendelian randomization method that accounts for pleiotropy and reverse causation, providing more reliable causal effect estimates and direction inference from observational genetic data.

Contribution

It extends Mendelian randomization by modeling pleiotropic effects and reverse causation within a Bayesian framework, improving causal inference accuracy.

Findings

BayesMR effectively accounts for pleiotropy and reverse causation.

The method provides a posterior distribution for causal effects, quantifying uncertainty.

BayesMR improves the reliability of causal direction inference.

Abstract

The use of genetic variants as instrumental variables - an approach known as Mendelian randomization - is a popular epidemiological method for estimating the causal effect of an exposure (phenotype, biomarker, risk factor) on a disease or health-related outcome from observational data. Instrumental variables must satisfy strong, often untestable assumptions, which means that finding good genetic instruments among a large list of potential candidates is challenging. This difficulty is compounded by the fact that many genetic variants influence more than one phenotype through different causal pathways, a phenomenon called horizontal pleiotropy. This leads to errors not only in estimating the magnitude of the causal effect but also in inferring the direction of the putative causal link. In this paper, we propose a Bayesian approach called BayesMR that is a generalization of the Mendelian randomization technique in which we allow for pleiotropic effects and, crucially, for the possibility of reverse causation. The output of the method is a posterior distribution over the target causal effect, which provides an immediate and easily interpretable measure of the uncertainty in the estimation. More importantly, we use Bayesian model averaging to determine how much more likely the inferred direction is relative to the reverse direction.