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The results from Genome-Wide Association Studies (GWAS) on thousands of phenotypes provide an unprecedented opportunity to infer the causal effect of one phenotype (exposure) on another (outcome). Mendelian randomization (MR), an…

Methodology · Statistics 2019-04-30 Jia Zhao , Jingsi Ming , Xianghong Hu , Gang Chen , Jin Liu , Can Yang

Background: Mendelian randomization (MR) is a useful approach to causal inference from observational studies when randomised controlled trials are not feasible. However, study heterogeneity of two association studies required in MR is often…

Methodology · Statistics 2021-12-16 Linyi Zou , Hui Guo , Carlo Berzuini

Mendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine-mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be…

Methodology · Statistics 2017-07-10 Stephen Burgess , Verena Zuber , Elsa Valdes-Marquez , Benjamin B Sun , Jemma C Hopewell

Mendelian randomization is a powerful tool for causal inference in observational studies. The two-sample summary-data design, which estimates genetic associations with exposures and outcomes in separate cohorts, is the most widely used…

Methodology · Statistics 2026-04-29 Dingke Tang , Xuming He , Shu Yang

In two-sample Mendelian randomization (MR), Egger regression is widely used as a sensitivity analysis when directional pleiotropy is detected. However, the increasing complexity of modern MR studies, characterized by many weak instruments,…

Methodology · Statistics 2025-07-15 Youpeng Su , Yilei Ma , Ping Yin , Peng Wang

The Egger intercept (EI) test is a widely used tool to detect horizontal pleiotropy in two-sample summary-data Mendelian randomization. A significant EI test suggests that either the average pleiotropic effect differs from zero (i.e.,…

Methodology · Statistics 2026-05-28 Yilei Ma , Youpeng Su , Xin Liu , Xuanye Cui , Ping Yin , Peng Wang

Our Bayesian approach to Mendelian Randomisation uses multiple instruments to assess the putative causal effect of an exposure on an outcome. The approach is robust to violations of the (untestable) Exclusion Restriction condition, and…

Statistics Theory · Mathematics 2017-02-01 Carlo Berzuini , Hui Guo , Stephen Burgess , Luisa Bernardinelli

Multivariable Mendelian Randomization (MVMR) estimates the direct causal effects of multiple risk factors on an outcome using genetic variants as instruments. The growing availability of summary-level genetic data has created opportunities…

Methodology · Statistics 2025-11-18 Yinxiang Wu , Neil M. Davies , Ting Ye

Multivariate Mendelian randomization (MVMR) is a statistical technique that uses sets of genetic instruments to estimate the direct causal effects of multiple exposures on an outcome of interest. At genomic loci with pleiotropic gene…

Methodology · Statistics 2024-09-23 Mariyam Khan , Adriaan-Alexander Ludl , Sean Bankier , Johan Bjorkegren , Tom Michoel

Developments in genome-wide association studies and the increasing availability of summary genetic association data have made the application of two-sample Mendelian Randomization (MR) with summary data increasingly popular. Conventional…

Methodology · Statistics 2023-02-22 Xinwei Ma , Jingshen Wang , Chong Wu

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…

Applications · Statistics 2022-06-15 Daniel Iong , Qingyuan Zhao , Yang Chen

Mendelian randomization is an instrumental variable method that utilizes genetic information to investigate the causal effect of a modifiable exposure on an outcome. In most cases, the exposure changes over time. Understanding the…

Methodology · Statistics 2024-03-11 Haodong Tian , Ashish Patel , Stephen Burgess

Mendelian randomization (MR) considers using genetic variants as instrumental variables (IVs) to infer causal effects in observational studies. However, the validity of causal inference in MR can be compromised when the IVs are potentially…

Methodology · Statistics 2024-02-06 Ziya Xu , Sai Li

Mendelian randomization (MR) uses genetic variants as instrumental variables to make causal claims. Standard MR approaches typically report a single population-averaged estimate, limiting their ability to explore effect heterogeneity or…

Methodology · Statistics 2025-07-16 Stephen Burgess , Benjamin A R Woolf , Amy M Mason

We consider the challenging problem of estimating causal effects from purely observational data in the bi-directional Mendelian randomization (MR), where some invalid instruments, as well as unmeasured confounding, usually exist. To address…

Methodology · Statistics 2024-07-15 Feng Xie , Zhen Yao , Lin Xie , Yan Zeng , Zhi Geng

Our approach to Mendelian Randomization (MR) analysis is designed to increase reproducibility of causal effect "discoveries" by: (i) using a Bayesian approach to inference; (ii) replacing the point null hypothesis with a region of practical…

Methodology · Statistics 2022-08-11 Linyi Zou , Teresa Fazia , Hui Guo , Carlo Berzuini

Multivariable Mendelian randomization estimates the causal effect of multiple exposures on an outcome, typically using summary statistics of genetic variant associations. However, exposures of interest in Mendelian randomization…

Methodology · Statistics 2022-03-17 Jiazheng Zhu , Stephen Burgess , Andrew J. Grant

Mendelian randomization uses genetic variants to make causal inferences about a modifiable exposure. Subject to a genetic variant satisfying the instrumental variable assumptions, an association between the variant and outcome implies a…

Methodology · Statistics 2018-04-17 Stephen Burgess , Jeremy A Labrecque

Many Mendelian randomization (MR) papers have been conducted only in people of European ancestry, limiting transportability of results to the global population. Expanding MR to diverse ancestry groups is essential to ensure equitable…

The recently developed rerandomized inverse variance weighted (RIVW) estimator provides a simple and efficient framework to break the winner's curse in two-sample Mendelian randomization (MR). However, this method has ignored the possible…

Methodology · Statistics 2026-03-09 Xin Liu , Ping Yin , Peng Wang