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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

Motivation: Mendelian randomization (MR) infers causal relationships between exposures and outcomes using genetic variants as instrumental variables. Typically, MR considers only a pair of exposure and outcome at a time, limiting its…

Applications · Statistics 2025-10-14 Bitan Sarkar , Yang Ni

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…

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 (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 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

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

Omics biomarkers play a pivotal role in personalized medicine by providing molecular-level insights into the etiology of diseases, guiding precise diagnostics, and facilitating targeted therapeutic interventions. Recent advancements in…

Applications · Statistics 2024-02-21 Minhao Yao , Zhonghua Liu

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

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

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…

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

Integrating data from multiple heterogeneous sources has become increasingly popular to achieve a large sample size and diverse study population. This paper reviews development in causal inference methods that combines multiple datasets…

Methodology · Statistics 2021-10-05 Xu Shi , Ziyang Pan , Wang Miao

Mendelian Randomization is a widely used instrumental variable method for assessing causal effects of lifelong exposures on health outcomes. Many exposures, however, have causal effects that vary across the life course and often influence…

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

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

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

It is widely acknowledged that there is a diversity problem in genomics stemming from the vast underrepresentation of non-European genetic ancestry populations. While many challenges exist to address this gap, a major complicating factor is…

Other Quantitative Biology · Quantitative Biology 2022-05-03 Daphne O. Martschenko , Hannah Wand , Jennifer L. Young , Genevieve L. Wojcik

Recent work has made important contributions in the development of causally-interpretable meta-analysis. These methods transport treatment effects estimated in a collection of randomized trials to a target population of interest. Ideally,…

Methodology · Statistics 2023-02-08 Justin M. Clark , Kollin W. Rott , James S. Hodges , Jared D. Huling

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