ArticleScientific reports2021
Gene-environment dependencies lead to collider bias in models with polygenic scores.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Gene-environment interplay explaining individual variation in BMI outcomes: a systematic review and meta-analysis of studies using polygenic indices.International journal of obesity (2005) · 2026Pooled it
- Cross-National and Cross-Generational Evidence That Educational Attainment May Slow the Pace of Aging in European-Descent Individuals.The journals of gerontology. Series B, Psychological sciences and social sciences · 2023Pooled it
- Psychiatric and substance use disorder polygenic scores are associated with the exposome in youth.European child & adolescent psychiatry · 2026Article
- Polygenic risk scores in human genetics for study design discovery and translation.Human genetics · 2026Review
- Ancestry-Calibrated Polygenic Risk Scores Predict PTSD Trajectories in Recent Trauma Survivors and Interact with Neighborhood Resources.medRxiv : the preprint server for health sciences · 2026Article
- Genetically Informed Research Designs in Perinatal Pharmacoepidemiology: A Methodological Overview.Drug safety · 2026Review
- Interaction Between Genetic Risk and Parental Feeding Practices in the Prediction of Overweight Across Adolescence.Obesity (Silver Spring, Md.) · 2026Article
- Polygenic risk factors for comorbid diagnoses in individuals with substance use disorders: A phenome-wide survival analysis.Psychological medicine · 2026Article
- Adolescent pain reports share genetic overlap with adult chronic pain conditions: A polygenic score analysis using the ABCD study.The journal of pain · 2026Article
- Non-cognitive skills mediate education-related polygenic score associations with academic achievement across development.Nature communications · 2026Article
- Article
- Community physical activity environments and physical activity levels among older adults: a hierarchical analysis of environmental dimensions.Frontiers in public health · 2026Article
- The impact of collider bias on genetic prediction in psychotic disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Family income and polygenic scores are independently but not interactively associated with cognitive performance among youth genetically similar to European reference populations.Development and psychopathology · 2025Article
- Complementary MR measures of white matter and their relation to cardiovascular health and cognition.Scientific reports · 2025Article
- Pathway polygenic risk scores (pPRS) for the analysis of gene-environment interaction.PLoS genetics · 2025Article
- From genetic disposition to academic achievement: The mediating role of non-cognitive skills across development.bioRxiv : the preprint server for biology · 2025Article
- Genetic associations between non-cognitive skills and academic achievement over development.Nature human behaviour · 2024Article
- Clinical, genomic, and neurophysiological correlates of lifetime suicide attempts among individuals with an alcohol use disorder.medRxiv : the preprint server for health sciences · 2024Article
- Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding.Environmental science & technology · 2024Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The application of polygenic scores has transformed our ability to investigate whether and how genetic and environmental factors jointly contribute to the variation of complex traits. Modelling the complex interplay between genes and environment, however, raises serious methodological challenges. Here we illustrate the largely unrecognised impact of gene-environment dependencies on the identification of the effects of genes and their variation across environments. We show that controlling for heritable covariates in regression models that include polygenic scores as independent variables introduces endogenous selection bias when one or more of these covariates depends on unmeasured factors that also affect the outcome. This results in the problem of conditioning on a collider, which in turn leads to spurious associations and effect sizes. Using graphical and simulation methods we demonstrate that the degree of bias depends on the strength of the gene-covariate correlation and of hidden heterogeneity linking covariates with outcomes, regardless of whether the main analytic focus is mediation, confounding, or gene × covariate (commonly gene × environment) interactions. We offer potential solutions, highlighting the importance of causal inference. We also urge further caution when fitting and interpreting models with polygenic scores and non-exogenous environments or phenotypes and demonstrate how spurious associations are likely to arise, advancing our understanding of such results.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.