Lorincz-Comi, N. J. | Search bioRxiv

bioRxiv2023

simmr: An open-source tool to perform simulations in Mendelian Randomization

Mendelian Randomization (MR) has become a popular tool for inferring causality of risk factors on disease. There are currently over 45 different methods available to perform MR, reflecting this extremely active research area. It would be desirable to have a standard simulation environment to objectively evaluate the existing and future methods. We present simmr, an open-source software for performing simulations to evaluate the performance of MR methods in a range of scenarios encountered in practice. Researchers can directly modify the simmr source code so that the research community may arrive at a widely accepted frame-work for researchers to evaluate the performance of different MR methods.

bioinformatics↗

bioRxiv2023

MRBEE: A novel bias-corrected multivariable Mendelian Randomization method

Mendelian randomization (MR) is an instrumental variable approach used to infer causal relationships between exposures and outcomes and can apply to summary data from genome-wide association studies (GWAS). Since GWAS summary statistics are subject to estimation errors, most existing MR approaches suffer from measurement error bias, whose scale and direction are influenced by weak instrumental variables and GWAS sample overlap, respectively. We introduce MRBEE (MR using Bias-corrected Estimating Equation), a novel multivariable MR method capable of simultaneously removing measurement error bias and identifying horizontal pleiotropy. In simulations, we showed that MRBEE is capable of effectively removing measurement error bias in the presence of weak instrumental variables and sample overlap. In two independent real data analyses, we discovered that the causal effect of BMI on coronary artery disease risk is entirely mediated by blood pressure, and that existing MR methods may underestimate the causal effect of cannabis use disorder on schizophrenia risk compared to MRBEE. MRBEE possesses significant potential for advancing genetic research by providing a valuable tool to study causality between multiple risk factors and disease outcomes, particularly as a large number of GWAS summary statistics become publicly available.

genomics↗