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When genetic variants in a gene cluster are associated with a disease outcome, the causal pathway from the variants to the outcome can be difficult to disentangle. For example, the chemokine receptor gene cluster contains genetic variants…

Methodology · Statistics 2021-10-05 Fatima Batool , Ashish Patel , Dipender Gill , Stephen Burgess

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 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

Interactions between genes and environmental factors may play a key role in the etiology of many common disorders. Several regularized generalized linear models (GLMs) have been proposed for hierarchical selection of gene by environment…

Methodology · Statistics 2023-12-22 Julien St-Pierre , Karim Oualkacha , Julien St-Pierre

Standard logistic regression analysis of case-control data has low power to detect gene-environment interactions, but until recently it was the only method that could be used on complex polygenic data for which parametric distributional…

Methodology · Statistics 2020-10-13 Tianying Wang , Alex Asher

Multivariable Mendelian randomization (MVMR) uses genetic variants as instrumental variables to infer the direct effects of multiple exposures on an outcome. However, unlike univariable Mendelian randomization, MVMR often faces greater…

Methodology · Statistics 2025-08-19 Yinxiang Wu , Hyunseung Kang , Ting Ye

In the genomic analysis, it is significant while challenging to identify markers associated with cancer outcomes or phenotypes. Based on the biological mechanisms of cancers and the characteristics of datasets as well, this paper proposes a…

Methodology · Statistics 2022-11-30 Yang Li , Fan Wang , Rong Li , Yifan Sun

Methods utilizing instrumental variables have been a fundamental statistical approach to estimation in the presence of unmeasured confounding, usually occurring in non-randomized observational data common to fields such as economics and…

Methodology · Statistics 2022-10-06 Charles Spanbauer , Wei Pan

Variations in complex traits are influenced by multiple genetic variants, environmental risk factors, and their interactions. Though substantial progress has been made in identifying single genetic variants associated with complex traits,…

Genomics · Quantitative Biology 2025-08-22 Ming Li , Ruo-Sin Peng , Changshuai Wei , Qing Lu

In plant breeding and variety testing, there is an increasing interest in making use of environmental information to enhance predictions for new environments. Here, we will review linear mixed models that have been proposed for this…

Methodology · Statistics 2026-03-12 Maksym Hrachov , Hans-Peter Piepho , Niaz Md. Farhat Rahman , Waqas Ahmed Malik

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

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 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

In the past decade, the increased availability of genome-wide association studies summary data has popularized Mendelian Randomization (MR) for conducting causal inference. MR analyses, incorporating genetic variants as instrumental…

Methodology · Statistics 2025-08-26 Zhongming Xie , Wanheng Zhang , Jingshen Wang , Chong Wu

Mendelian randomization implemented through instrumental variable analysis is frequently discussed in causality and recently the number of applications on real data is increasing. However, there are very few discussions to address modern…

Applications · Statistics 2020-04-16 Azam Yazdani

It is becoming increasingly clear that complex interactions among genes and environmental factors play crucial roles in triggering complex diseases. Thus, understanding such interactions is vital, which is possible only through statistical…

Applications · Statistics 2020-05-04 Durba Bhattacharya , Sourabh Bhattacharya

One component of precision medicine is to construct prediction models with their predictive ability as high as possible, e.g. to enable individual risk prediction. In genetic epidemiology, complex diseases have a polygenic basis and a…

Machine Learning · Statistics 2019-01-28 Damian Gola , Inke R. König

High-dimensional biomarkers such as genomics are increasingly being measured in randomized clinical trials. Consequently, there is a growing interest in developing methods that improve the power to detect biomarker-treatment interactions.…

Methodology · Statistics 2021-04-30 Jixiong Wang , Ashish Patel , James M. S. Wason , Paul J. Newcombe

Mendelian randomization (MR) has been a popular method in genetic epidemiology to estimate the effect of an exposure on an outcome using genetic variants as instrumental variables (IV), with two-sample summary-data MR being the most…

Methodology · Statistics 2021-06-08 Sheng Wang , Hyunseung Kang

Analysis of observational studies increasingly confronts the challenge of determining which of a possibly high-dimensional set of available covariates are required to satisfy the assumption of ignorable treatment assignment for estimation…

Methodology · Statistics 2022-03-23 Chanmin Kim , Mauricio Tec , Corwin M Zigler