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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 (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

When making causal inferences, post-treatment confounders complicate analyses of time-varying treatment effects. Conditioning on these variables naively to estimate marginal effects may inappropriately block causal pathways and may induce…

Applications · Statistics 2019-04-02 Xiang Zhou , Geoffrey T. Wodtke

Estimating the causal effect of an exposure on an outcome is an important task in many economical and biological studies. Mendelian randomization, in particular, uses genetic variants as instruments to estimate causal effects in…

Methodology · Statistics 2017-06-06 Sai Li

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

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

We often seek to estimate the causal effect of an exposure on a particular outcome in both randomized and observational settings. One such estimation method is the covariate-adjusted residuals estimator, which was designed for individually…

Methodology · Statistics 2019-10-28 Stephen A. Lauer , Nicholas G. Reich , Laura B. Balzer

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

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

Joint misclassification of exposure and outcome variables can lead to considerable bias in epidemiological studies of causal exposure-outcome effects. In this paper, we present a new maximum likelihood based estimator for the marginal…

Methodology · Statistics 2019-01-16 Bas B. L. Penning de Vries , Maarten van Smeden , Rolf H. H. Groenwold

A major limitation of machine learning (ML) prediction models is that they recover associational, rather than causal, predictive relationships between variables. In high-stakes automation applications of ML this is problematic, as the model…

Machine Learning · Computer Science 2025-11-04 Jianqiao Mao , Max A. Little

Propensity score methods are increasingly being used to reduce estimation bias of treatment effects for observational studies. Previous research has shown that propensity score methods consistently estimate the marginal hazard ratio for…

Methodology · Statistics 2019-11-19 Haodi Liang , Cecilia Cotton

We consider the problem of estimating a structured multivariate density, subject to Markov conditions implied by an undirected graph. In the worst case, without Markovian assumptions, this problem suffers from the curse of dimensionality.…

Machine Learning · Statistics 2024-10-11 Robert A. Vandermeulen , Wai Ming Tai , Bryon Aragam

With multiple outcomes in empirical research, a common strategy is to define a composite outcome as a weighted average of the original outcomes. However, the choices of weights are often subjective and can be controversial. We propose an…

Methodology · Statistics 2025-09-17 Wei Zhang , Qizhai Li , Peng Ding

Background: Mendelian randomization (MR) is a useful approach to causal inference from observational studies when randomised controlled trials are not feasible. However, study heterogeneity of two association studies required in MR is often…

Methodology · Statistics 2021-12-16 Linyi Zou , Hui Guo , Carlo Berzuini

Contrasting marginal counterfactual survival curves across treatment arms is an effective and popular approach for inferring the causal effect of an intervention on a right-censored time-to-event outcome. A key challenge to drawing such…

Methodology · Statistics 2022-04-29 Andrew Ying , Yifan Cui , Eric J. Tchetgen Tchetgen

Case-control studies are designed towards studying associations between risk factors and a single, primary outcome. Information about additional, secondary outcomes is also collected, but association studies targeting such secondary…

Methodology · Statistics 2014-07-17 Tamar Sofer , Marilyn C. Cornelis , Peter Kraft , Eric J. Tchetgen Tchetgen

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

We develop new methods to integrate experimental and observational data in causal inference. While randomized controlled trials offer strong internal validity, they are often costly and therefore limited in sample size. Observational data,…

Econometrics · Economics 2025-11-04 Xuelin Yang , Licong Lin , Susan Athey , Michael I. Jordan , Guido W. Imbens

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