ArticleCirculation. Genomic and precision medicine2021
Interactions Between Enhanced Polygenic Risk Scores and Lifestyle for Cardiovascular Disease, Diabetes, and Lipid Levels.
Article in Circulation. Genomic and precision medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Association Between Serum Lipids and Survival in Patients With Amyotrophic Lateral Sclerosis: A Meta-analysis and Population-Based Study.Neurology · 2023Pooled it
- Polygenic Risk Scores disclosure for cardiovascular prevention: Protocol of the Personalized HeartCare (PHC) trial.PloS one · 2026Trial
- Development and Validation of a Clinical Polygenic Risk Report in U.S.-Based Health Systems for 8 Cardiovascular Conditions.Journal of the American College of Cardiology · 2026Article
- Inherited risk of coronary artery disease: redefining care with imaging and genetics.Nature reviews. Cardiology · 2026Review
- Pervasive interactions between exposures and polygenic risk can inform more effective clinical and behavioral interventions.Nature genetics · 2026Article
- Associations between Dietary Selenium Intake and Risk of Incident Arthritis: Based on UK Biobank WebQ Assessment (2009-2012).Biological trace element research · 2026Article
- Sex-stratified polygenic risk scores for coronary artery disease incidence: Insights from a 20-year cohort study.BMC cardiovascular disorders · 2026Article
- Metabolic polygenic risk scores for prediction of obesity, type 2 diabetes, and related morbidities.Cell metabolism · 2026Article
- Polygenic predisposition modifies the associations of fish oil supplementation with circulating omega-3 fatty acids: a cross-sectional gene-diet interaction study in UK Biobank.medRxiv : the preprint server for health sciences · 2026Article
- Associations of vegetarianism with circulating lipids across varying genetic capacity: a cross-sectional Polygenic Score-by-Vegetarianism interaction study in UK Biobank.medRxiv : the preprint server for health sciences · 2026Article
- Influence of treatment, genetic predisposition, and lifestyle on cardiovascular risk factors among cancer survivors.Journal of the National Cancer Institute · 2026Article
- Joint associations of cardiovascular polygenic risk and a health-related risk profile with incident cardiovascular disease among adults with depression: a UK Biobank study.Frontiers in endocrinology · 2026Article
- Selected Genes Associated With CVD-Related Diseases, Pathways, and Nutrigenetics.Journal of lipid and atherosclerosis · 2026Review
- Incorporating additive genetic effects and linkage disequilibrium information to discover gene-environment interactions using BV-LDER-GE.Genome biology · 2025Article
- PIGEON: a statistical framework for estimating gene-environment interaction for polygenic traits.Nature human behaviour · 2025Article
- Comprehensive interaction modeling with machine learning improves prediction of disease risk in the UK Biobank.Nature communications · 2025Article
- Interaction between genetic risk and comorbid conditions in endometriosis.HGG advances · 2025Article
- Meta-prediction of coronary artery disease risk.Nature medicine · 2025Article
- Impact of lifestyle factors on adult-onset asthma in genetically high-risk individuals.Journal of global health · 2025Article
- Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes.Circulation · 2025Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundBoth lifestyle and genetic factors confer risk for cardiovascular diseases, type 2 diabetes, and dyslipidemia. However, the interactions between these 2 groups of risk factors were not comprehensively understood due to previous poor estimation of genetic risk. Here we set out to develop enhanced polygenic risk scores (PRS) and systematically investigate multiplicative and additive interactions between PRS and lifestyle for coronary artery disease, atrial fibrillation, type 2 diabetes, total cholesterol, triglyceride, and LDL-cholesterol.
methodsOur study included 276 096 unrelated White British participants from the UK Biobank. We investigated several PRS methods (P+T, LDpred, PRS continuous shrinkage, and AnnoPred) and showed that AnnoPred achieved consistently improved prediction accuracy for all 6 diseases/traits. With enhanced PRS and combined lifestyle status categorized by smoking, body mass index, physical activity, and diet, we investigated both multiplicative and additive interactions between PRS and lifestyle using regression models.
resultsWe observed that healthy lifestyle reduced disease incidence by similar multiplicative magnitude across different PRS groups. The absolute risk reduction from lifestyle adherence was, however, significantly greater in individuals with higher PRS. Specifically, for type 2 diabetes, the absolute risk reduction from lifestyle adherence was 12.4% (95% CI, 10.0%-14.9%) in the top 1% PRS versus 2.8% (95% CI, 2.3%-3.3%) in the bottom PRS decile, leading to a ratio of >4.4. We also observed a significant interaction effect between PRS and lifestyle on triglyceride level.
conclusionsBy leveraging functional annotations, AnnoPred outperforms state-of-the-art methods on quantifying genetic risk through PRS. Our analyses based on enhanced PRS suggest that individuals with high genetic risk may derive similar relative but greater absolute benefit from lifestyle adherence.
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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.