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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

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

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

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 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

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

When genetic variants in a gene cluster are associated with a disease outcome, the causal pathway from the variants to the outcome can be difficult to disentangle. For example, the chemokine receptor gene cluster contains genetic variants…

Methodology · Statistics 2021-10-05 Fatima Batool , Ashish Patel , Dipender Gill , Stephen Burgess

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 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

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 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

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

The quantile residual lifetime (QRL) regression is an attractive tool for assessing covariate effects on the distribution of residual life expectancy, which is often of interest in clinical studies. When the study subjects are exposed to…

Methodology · Statistics 2025-03-04 Tonghui Yu , Liming Xiang , Jong-Hyeon Jeong

It is known that the estimating equations for quantile regression (QR) can be solved using an EM algorithm in which the M-step is computed via weighted least squares, with weights computed at the E-step as the expectation of independent…

Methodology · Statistics 2021-08-26 Haim Bar , James Booth , Martin T. Wells

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) 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 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…

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

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

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