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Mendelian randomization (MR) has become a popular approach to study causal effects by using genetic variants as instrumental variables. We propose a new MR method, GENIUS-MAWII, which simultaneously addresses the two salient phenomena that…

Methodology · Statistics 2024-02-27 Ting Ye , Zhonghua Liu , Baoluo Sun , Eric Tchetgen Tchetgen

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

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

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 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

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 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

The use of genetic variants as instrumental variables - an approach known as Mendelian randomization - is a popular epidemiological method for estimating the causal effect of an exposure (phenotype, biomarker, risk factor) on a disease or…

Methodology · Statistics 2020-12-21 Ioan Gabriel Bucur , Tom Claassen , Tom Heskes

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

Background In a study performed on multiplex Multiple Sclerosis (MS) Sardinian families to identify disease causing plasma proteins, application of Mendelian Randomization (MR) methods encounters difficulties due to relatedness of…

Multivariable Mendelian randomization (MVMR) uses genetic variants as instrumental variables to infer the direct effects of multiple exposures on an outcome. However, unlike univariable Mendelian randomization, MVMR often faces greater…

Methodology · Statistics 2025-08-19 Yinxiang Wu , Hyunseung Kang , Ting Ye

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

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

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

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

The instrumental variable (IV) design is a common approach to address hidden confounding bias. For validity, an IV must impact the outcome only through its association with the treatment. In addition, IV identification has required a…

Mendelian randomization (MR) has become a popular approach to study the effect of a modifiable exposure on an outcome by using genetic variants as instrumental variables. A challenge in MR is that each genetic variant explains a relatively…

Methodology · Statistics 2020-10-13 Ting Ye , Jun Shao , Hyunseung Kang

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

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

We expand Mendelian Randomization (MR) methodology to deal with randomly missing data on either the exposure or the outcome variable, and furthermore with data from nonindependent individuals (eg components of a family). Our method rests on…

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