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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

Recent advances in genotyping technology have delivered a wealth of genetic data, which is rapidly advancing our understanding of the underlying genetic architecture of complex diseases. Mendelian Randomization (MR) leverages such genetic…

Methodology · Statistics 2023-12-19 Wenhao Cao , Saonli Basu

Mendelian randomization is a powerful tool for inferring the presence, or otherwise, of causal effects from observational data. However, the nature of genetic variants is such that pleiotropy remains a barrier to valid causal effect…

Methodology · Statistics 2021-08-04 Andrew J. Grant , Stephen Burgess

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

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

Methods have been developed for Mendelian randomization that can obtain consistent causal estimates while relaxing the instrumental variable assumptions. These include multivariable Mendelian randomization, in which a genetic variant may be…

Methodology · Statistics 2017-08-02 Jessica M. B. Rees , Angela Wood , Stephen Burgess

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

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

The method of multivariable Mendelian randomization uses genetic variants to instrument multiple exposures, to estimate the effect that a given exposure has on an outcome conditional on all other exposures included in a linear model.…

Methodology · Statistics 2024-08-20 Ashish Patel , James Lane , Stephen Burgess

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

Empirical researchers are often interested in not only whether a treatment affects an outcome of interest, but also how the treatment effect arises. Causal mediation analysis provides a formal framework to identify causal mechanisms through…

Econometrics · Economics 2022-02-01 Bora Kim

Mendelian randomization is the use of genetic variants as instrumental variables to assess whether a risk factor is a cause of a disease outcome. Increasingly, Mendelian randomization investigations are conducted on the basis of summarized…

Applications · Statistics 2015-12-15 Stephen Burgess , Jack Bowden

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

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

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

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

Mendelian randomization (MR) is a powerful approach to examine the causal relationships between health risk factors and outcomes from observational studies. Due to the proliferation of genome-wide association studies (GWASs) and abundant…

Methodology · Statistics 2020-09-02 Qing Cheng , Baoluo Sun , Yingcun Xia , Jin Liu

Tailoring treatments to individual needs is a central goal in fields such as medicine. A key step toward this goal is estimating Heterogeneous Treatment Effects (HTE) - the way treatments impact different subgroups. While crucial, HTE…

Machine Learning · Statistics 2025-07-30 Tomer Meir , Uri Shalit , Malka Gorfine

Estimating the causal effect of an exposure on an outcome is an important task in many economical and biological studies. Mendelian randomization, in particular, uses genetic variants as instruments to estimate causal effects in…

Methodology · Statistics 2017-06-06 Sai Li

The instrumental variables (IV) method is a method for making causal inferences about the effect of a treatment based on an observational study in which there are unmeasured confounding variables. The method requires a valid IV, a variable…

Methodology · Statistics 2014-08-19 Dylan Small , Zhiqiang Tan , Scott Lorch , Alan Brookhart