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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 is a powerful tool for causal inference in observational studies. The two-sample summary-data design, which estimates genetic associations with exposures and outcomes in separate cohorts, is the most widely used…

Methodology · Statistics 2026-04-29 Dingke Tang , Xuming He , Shu Yang

Instrumental variable methods provide useful tools for inferring causal effects in the presence of unmeasured confounding. To apply these methods with large-scale data sets, a major challenge is to find valid instruments from a possibly…

Methodology · Statistics 2024-09-24 Xinyi Zhang , Linbo Wang , Stanislav Volgushev , Dehan Kong

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

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

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

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

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 (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

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

Instrumental variable methods provide a powerful approach to estimating causal effects in the presence of unobserved confounding. But a key challenge when applying them is the reliance on untestable "exclusion" assumptions that rule out any…

Methodology · Statistics 2020-06-23 Jason Hartford , Victor Veitch , Dhanya Sridhar , Kevin Leyton-Brown

Instrumental variable methods are widely used for inferring the causal effect in the presence of unmeasured confounders. Existing instrumental variable methods for nonlinear outcome models require stringent identifiability conditions. This…

Methodology · Statistics 2022-07-01 Sai Li , Zijian Guo

The use of instrumental variables for estimating the effect of an exposure on an outcome is popular in econometrics, and increasingly so in epidemiology. This increasing popularity may be attributed to the natural occurrence of instrumental…

Methodology · Statistics 2016-08-03 T. Martinussen , S. Vansteelandt , E. J. Tchetgen Tchetgen , D. M. Zucker

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…

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

Instrumental variables are a popular tool to infer causal effects under unobserved confounding, but choosing suitable instruments is challenging in practice. We propose gIVBMA, a Bayesian model averaging procedure that addresses this…

Methodology · Statistics 2026-03-02 Gregor Steiner , Mark Steel

We develop an empirical Bayes procedure for estimating the cell means in an unbalanced, two-way additive model with fixed effects. We employ a hierarchical model, which reflects exchangeability of the effects within treatment and within…

Methodology · Statistics 2016-05-30 Lawrence D. Brown , Gourab Mukherjee , Asaf Weinstein

Mendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine-mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be…

Methodology · Statistics 2017-07-10 Stephen Burgess , Verena Zuber , Elsa Valdes-Marquez , Benjamin B Sun , Jemma C Hopewell

Parameter estimates for associated genetic variants, report ed in the initial discovery samples, are often grossly inflated compared to the values observed in the follow-up replication samples. This type of bias is a consequence of the…

Applications · Statistics 2011-04-15 Lizhen Xu , Radu V. Craiu , Lei Sun

In this paper, we discuss causal inference on the efficacy of a treatment or medication on a time-to-event outcome with competing risks. Although the treatment group can be randomized, there can be confoundings between the compliance and…

Methodology · Statistics 2016-12-06 Cheng Zheng , Ran Dai , Parameswaran Hari , Mei-Jie Zhang