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Mendelian randomization (MR) has become an essential tool for causal inference in biomedical and public health research. By using genetic variants as instrumental variables, MR helps address unmeasured confounding and reverse causation,…

Methodology · Statistics 2025-11-04 Minhao Yao , Anqi Wang , Xihao Li , Zhonghua Liu

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

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

Mendelian Randomisation (MR) uses genetic variants as instrumental variables to infer causal effects of exposures on an outcome. One key assumption of MR is that the genetic variants used as instrumental variables are independent of the…

Methodology · Statistics 2025-02-21 Maximilian M Mandl , Anne-Laure Boulesteix , Stephen Burgess , Verena Zuber

Mendelian randomization (MR) is a natural experimental design based on the random transmission of genes from parents to offspring. However, this inferential basis is typically only implicit or used as an informal justification. As…

Methodology · Statistics 2023-04-19 Matthew J Tudball , George Davey Smith , Qingyuan Zhao

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 (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 is the use of genetic variants to make causal inferences from observational data. The field is currently undergoing a revolution fuelled by increasing numbers of genetic variants demonstrated to be associated with…

Methodology · Statistics 2018-08-31 Stephen Burgess , Jack Bowden , Frank Dudbridge , Simon G Thompson

Mendelian randomization (MR) is a method of exploiting genetic variation to unbiasedly estimate a causal effect in presence of unmeasured confounding. MR is being widely used in epidemiology and other related areas of population science. In…

Applications · Statistics 2019-01-03 Qingyuan Zhao , Jingshu Wang , Gibran Hemani , Jack Bowden , Dylan S. Small

Mendelian randomization (MR) is a widely-used method to estimate the causal relationship between a risk factor and disease. A fundamental part of any MR analysis is to choose appropriate genetic variants as instrumental variables.…

Methodology · Statistics 2023-04-26 Ashish Patel , Francis J. DiTraglia , Verena Zuber , Stephen Burgess

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 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

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

Background: Mendelian randomization (MR) has been widely applied to causal inference in medical research. It uses genetic variants as instrumental variables (IVs) to investigate putative causal relationship between an exposure and an…

Methodology · Statistics 2020-11-04 Linyi Zou , Hui Guo , Carlo Berzuini

Mendelian randomization (MR) is a powerful method that uses genetic variants as instrumental variables (IVs) to infer the causal effect of a modifiable exposure on an outcome. Although recent years have seen many extensions of basic MR…

Methodology · Statistics 2022-03-15 Sai Li , Ting Ye

Mediation analysis is a powerful tool for studying causal pathways between exposure, mediator, and outcome variables of interest. While classical mediation analysis using observational data often requires strong and sometimes unrealistic…

Methodology · Statistics 2024-05-20 Rita Qiuran Lyu , Chong Wu , Xinwei Ma , Jingshen Wang

Observed differences in mean phenotypic values across human groups have attracted renewed interest with the rise of large-scale genomic studies and polygenic risk prediction. However, the genetic basis of these differences is far more…

Populations and Evolution · Quantitative Biology 2026-05-25 Nicole Kleman , Meng Lin , Christopher R. Gignoux , Arslan A. Zaidi

Mendelian randomization is the use of genetic variants to assess the existence of a causal relationship between a risk factor and an outcome of interest. Here, we focus on two-sample summary-data Mendelian randomization analyses with many…

Quantitative Methods · Quantitative Biology 2022-09-16 Apostolos Gkatzionis , Stephen Burgess , Paul J. Newcombe

Mendelian randomization (MR) is an epidemiological method that can be used to strengthen causal inference regarding the relationship between a modifiable environmental exposure and a medically relevant trait and to estimate the magnitude of…

Quantitative Methods · Quantitative Biology 2023-08-30 David M Evans , George Davey Smith , Gunn-Helen Moen

Valid estimation of a causal effect using instrumental variables requires that all of the instruments are independent of the outcome conditional on the risk factor of interest and any confounders. In Mendelian randomization studies with…

Methodology · Statistics 2020-11-23 Andrew J. Grant , Stephen Burgess
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