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Our approach to Mendelian Randomization (MR) analysis is designed to increase reproducibility of causal effect "discoveries" by: (i) using a Bayesian approach to inference; (ii) replacing the point null hypothesis with a region of practical…

Methodology · Statistics 2022-08-11 Linyi Zou , Teresa Fazia , Hui Guo , Carlo Berzuini

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…

Risk evaluation to identify individuals who are at greater risk of cancer as a result of heritable pathogenic variants is a valuable component of individualized clinical management. Using principles of Mendelian genetics, Bayesian…

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

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

Multivariate Mendelian randomization (MVMR) is a statistical technique that uses sets of genetic instruments to estimate the direct causal effects of multiple exposures on an outcome of interest. At genomic loci with pleiotropic gene…

Methodology · Statistics 2024-09-23 Mariyam Khan , Adriaan-Alexander Ludl , Sean Bankier , Johan Bjorkegren , Tom Michoel

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

Selection bias is a common concern in epidemiologic studies. In the literature, selection bias is often viewed as a missing data problem. Popular approaches to adjust for bias due to missing data, such as inverse probability weighting, rely…

Mendelian randomization (MR) is a widely used tool for causal inference in the presence of unmeasured confounders, which uses single nucleotide polymorphisms (SNPs) as instrumental variables to estimate causal effects. However, SNPs often…

Methodology · Statistics 2025-04-29 Ruoyu Wang , Haoyu Zhang , Xihong Lin

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

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

Various statistical methods important for genetic analysis are considered and developed. Namely, we concentrate on the multifactor dimensionality reduction, logic regression, random forests and stochastic gradient boosting. These methods…

Probability · Mathematics 2011-06-29 Alexander Bulinski , Oleg Butkovsky , Alexey Shashkin , Pavel Yaskov

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 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

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

Variable selection has played a critical role in modern statistical learning and scientific discoveries. Numerous regularization and Bayesian variable selection methods have been developed in the past two decades for variable selection, but…

Methodology · Statistics 2024-03-04 Travis Canida , Hongjie Ke , Shuo Chen , Zhenayo Ye , Tianzhou Ma

Subgroup analysis is a frequently used tool for evaluating heterogeneity of treatment effect and heterogeneity in treatment harm across observed baseline patient characteristics. While treatment efficacy and adverse event measures are often…

Applications · Statistics 2018-08-14 Nicholas C. Henderson , Ravi Varadhan

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

Instrumental variables have been widely used for estimating the causal effect between exposure and outcome. Conventional estimation methods require complete knowledge about all the instruments' validity; a valid instrument must not have a…

Methodology · Statistics 2014-09-23 Hyunseung Kang , Anru Zhang , T. Tony Cai , Dylan S. Small

In many clinical and epidemiological studies, collecting longitudinal measurements together with time-to-event outcomes is essential. Accurately estimating the association between longitudinal markers and event risks, as well as identifying…