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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

Mendelian randomization (MR) is a statistical method exploiting genetic variants as instrumental variables to estimate the causal effect of modifiable risk factors on an outcome of interest. Despite wide uses of various popular two-sample…

Methodology · Statistics 2021-11-17 Anqi Wang , Zhonghua Liu

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

Mendelian randomization (MR) has become a popular approach to study causal effects by using genetic variants as instrumental variables. We propose a new MR method, GENIUS-MAWII, which simultaneously addresses the two salient phenomena that…

Methodology · Statistics 2024-02-27 Ting Ye , Zhonghua Liu , Baoluo Sun , Eric Tchetgen Tchetgen

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

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

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

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

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 widely used to uncover causal relationships in the presence of unmeasured confounders. However, most existing MR methods presuppose linear causality, risking bias when the true relationships are nonlinear,…

Methodology · Statistics 2025-08-05 Xinpei Wang , Tao Huang , Jinzhu Jia

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 is the use of genetic variants to make causal inferences from observational data. The field is currently undergoing a revolution fuelled by increasing numbers of genetic variants demonstrated to be associated with…

Methodology · Statistics 2018-08-31 Stephen Burgess , Jack Bowden , Frank Dudbridge , Simon G Thompson

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 an instrumental variable (IV) approach to infer causal relationships between exposures and outcomes with genome-wide association studies (GWAS) summary data. However, the multivariable inverse-variance…

Methodology · Statistics 2024-02-13 Yihe Yang , Noah Lorincz-Comi , Xiaofeng Zhu

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…

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

Mediation analysis is a powerful tool for studying causal pathways between exposure, mediator, and outcome variables of interest. While classical mediation analysis using observational data often requires strong and sometimes unrealistic…

Methodology · Statistics 2024-05-20 Rita Qiuran Lyu , Chong Wu , Xinwei Ma , Jingshen Wang

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