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Mendelian randomization is a widely-used method to estimate the unconfounded effect of an exposure on an outcome by using genetic variants as instrumental variables. Mendelian randomization analyses which use variants from a single genetic…

Methodology · Statistics 2024-02-20 Ashish Patel , Dipender Gill , Paul J. Newcombe , Stephen Burgess

In the past decade, the increased availability of genome-wide association studies summary data has popularized Mendelian Randomization (MR) for conducting causal inference. MR analyses, incorporating genetic variants as instrumental…

Methodology · Statistics 2025-08-26 Zhongming Xie , Wanheng Zhang , Jingshen Wang , Chong Wu

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

Mendelian randomization (MR) is a popular instrumental variable (IV) approach, in which one or several genetic markers serve as IVs that can sometimes be leveraged to recover valid inferences about a given exposure-outcome causal…

Methodology · Statistics 2021-08-10 Eric J. Tchetgen Tchetgen , BaoLuo Sun , Stefan Walter

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) is a prominent observational epidemiological research method designed to address unobserved confounding when estimating causal effects. However, core assumptions -- particularly the independence between…

Machine Learning · Computer Science 2026-02-24 Shimeng Huang , Matthew Robinson , Francesco Locatello

Mendelian randomization (MR) is a pivotal tool in genetics, genomics, and epidemiology, leveraging genetic variants as instrumental variables to infer causal relationships between exposures and outcomes. Traditional MR methods, while…

Methodology · Statistics 2026-01-15 Bitan Sarkar , Yuchao Jiang , Tian Ge , Yang Ni

Many diseases and traits involve a complex interplay between genes and environment, generating significant interest in studying gene-environment interaction through observational data. However, for lifestyle and environmental risk factors,…

Methodology · Statistics 2023-09-22 Malka Gorfine , Conghui Qu , Ulrike Peters , Li Hsu

Two-sample summary-data Mendelian randomization (MR) has become a popular research design to estimate the causal effect of risk exposures. With the sample size of GWAS continuing to increase, it is now possible to utilize genetic…

Applications · Statistics 2018-11-20 Qingyuan Zhao , Yang Chen , Jingshu Wang , Dylan S. Small

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

Standard Mendelian randomization analysis can produce biased results if the genetic variant defining the instrumental variable (IV) is confounded and/or has a horizontal pleiotropic effect on the outcome of interest not mediated by the…

Methodology · Statistics 2021-03-31 Zhonghua Liu , Ting Ye , Baoluo Sun , Mary Schooling , Eric Tchetgen Tchetgen

Mendelian randomization (MR) is a statistical method exploiting genetic variants as instrumental variables to estimate the causal effect of modifiable risk factors on an outcome of interest. Despite wide uses of various popular two-sample…

Methodology · Statistics 2021-11-17 Anqi Wang , Zhonghua Liu

Instrumental variables have been widely used for estimating the causal effect between exposure and outcome. Conventional estimation methods require complete knowledge about all the instruments' validity; a valid instrument must not have a…

Methodology · Statistics 2014-09-23 Hyunseung Kang , Anru Zhang , T. Tony Cai , Dylan S. Small

Mendelian randomization (MR) is a popular method in genetic epidemiology to estimate the effect of an exposure on an outcome by using genetic instruments. These instruments are often selected from a combination of prior knowledge from…

Methodology · Statistics 2019-11-12 Nan Bi , Hyunseung Kang , Jonathan Taylor

Mendelian randomization (MR) is widely used to uncover causal relationships in the presence of unmeasured confounders. However, most existing MR methods presuppose linear causality, risking bias when the true relationships are nonlinear,…

Methodology · Statistics 2025-08-05 Xinpei Wang , Tao Huang , Jinzhu Jia

Methods utilizing instrumental variables have been a fundamental statistical approach to estimation in the presence of unmeasured confounding, usually occurring in non-randomized observational data common to fields such as economics and…

Methodology · Statistics 2022-10-06 Charles Spanbauer , Wei Pan

In Mendelian randomization (MR) studies, genetic variants are used as instrumental variables (IVs) to investigate causal relationships between exposures and outcomes based on observational data. However, numerous genetic studies have shown…

Methodology · Statistics 2026-04-10 Julien St-Pierre , Archer Y. Yang , Mireille E. Schnitzer , Marc-André Legault

Mendelian randomization (MR) is a widely used tool for causal inference in the presence of unmeasured confounders, which uses single nucleotide polymorphisms (SNPs) as instrumental variables to estimate causal effects. However, SNPs often…

Methodology · Statistics 2025-04-29 Ruoyu Wang , Haoyu Zhang , Xihong Lin

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

Mendelian randomization (MR) is an instrumental variable (IV) approach to infer causal relationships between exposures and outcomes with genome-wide association studies (GWAS) summary data. However, the multivariable inverse-variance…

Methodology · Statistics 2024-02-13 Yihe Yang , Noah Lorincz-Comi , Xiaofeng Zhu