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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

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

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

Generative retrieval is an emerging approach in information retrieval that generates identifiers (IDs) of target data based on a query, providing an efficient alternative to traditional embedding-based retrieval methods. However, existing…

Information Retrieval · Computer Science 2025-06-09 Sungyeon Kim , Xinliang Zhu , Xiaofan Lin , Muhammet Bastan , Douglas Gray , Suha Kwak

In this paper, we introduce the Generalized Mixed Regularized Reduced Rank Regression model (GMR4), an extension of the GMR3 model designed to improve performance in high-dimensional settings. GMR3 is a regression method for a mix of…

Methodology · Statistics 2025-12-16 Lorenza Cotugno , Mark de Rooij , Roberta Siciliano

The recently developed rerandomized inverse variance weighted (RIVW) estimator provides a simple and efficient framework to break the winner's curse in two-sample Mendelian randomization (MR). However, this method has ignored the possible…

Methodology · Statistics 2026-03-09 Xin Liu , Ping Yin , Peng Wang

We investigate a simple objective for nonlinear instrumental variable (IV) regression based on a kernelized conditional moment restriction (CMR) known as a maximum moment restriction (MMR). The MMR objective is formulated by maximizing the…

Machine Learning · Computer Science 2023-02-10 Rui Zhang , Masaaki Imaizumi , Bernhard Schölkopf , Krikamol Muandet

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

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 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

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

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

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

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

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

In this study, we consider the problem of variable selection and estimation in high-dimensional linear regression models when the complete data are not accessible, but only certain marginal information or summary statistics are available.…

Applications · Statistics 2018-05-04 Jian Huang , Yuling Jiao , Jin Liu , Can Yang

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

Instrumental variable (IV) methods rely critically on the exclusion restriction, which is untestable in exactly-identified models under standard assumptions. We propose a framework combining IV analysis with the LiNGAM method to test this…

Econometrics · Economics 2026-03-17 Fernando Delbianco

Instrumental variables (IVs) are widely used to estimate causal effects in the presence of unobserved confounding between exposure and outcome. An IV must affect the outcome exclusively through the exposure and be unconfounded with the…

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