TwoStepCisMR: A Novel Method and R Package for Attenuating Bias in cis-Mendelian Randomization Analyses.

ABSTRACT: Mendelian randomisation (MR) is an increasingly popular method for strengthening causal inference in epidemiological studies. cis-MR in particular uses genetic variants in the gene region of a drug target protein as an instrumental variable to provide quasi-experimental evidence for on-target drug effects. A limitation of this framework is when the genetic variant is correlated to another variant that also effects the outcome of interest (confounding through linkage disequilibrium). Methods for correcting this bias, such as multivariable MR, struggle in a cis setting because of the high correlation among genetic variants. Here, through simulation experiments and an applied example considering the effect of interleukin 6 receptor signaling on coronary artery disease risk, we p

SUBMITTER: Woolf B 

PROVIDER: S-EPMC9498486 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature