ArticleClinical research in cardiology : official journal of the German Cardiac Society2023
Genetic and modifiable risk factors combine multiplicatively in common disease.
Article in Clinical research in cardiology : official journal of the German Cardiac Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Clinical utility of polygenic risk scores in cardiovascular disorders.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Aortic regurgitation is associated with African American and Asian race, smoking, renal disease, and numerous autoimmune diseases in addition to traditional cardiovascular risk factors but has lower risk with alcohol intake.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Article
- A new perspective on population genetics: Deciphering the relationship between genetic variants and disease prevalence in Psoriasis.PloS one · 2026Article
- Combined clinical, metabolomic, and polygenic scores for cardiovascular risk prediction.European heart journal · 2025Article
- Gene therapy and genome editing for lipoprotein disorders.European heart journal · 2025Review
- Interaction between genetic risk and comorbid conditions in endometriosis.HGG advances · 2025Article
- Appraisal of multiple polygenic risk scores to estimate the risk of myocardial infarction and coronary artery lesions.Communications medicine · 2025Article
- Unveiling new insights into migraine risk stratification using machine learning models of adjustable risk factors.The journal of headache and pain · 2025Article
- Article
- Review
- Ethical, Legal, and Social Implications of Gene-Environment Interaction Research.Genetic epidemiology · 2025Review
- Unraveling the Immune Web: Advances in SMI Capsular Fibrosis from Molecular Insights to Preclinical Breakthroughs.Biomolecules · 2024Review
- Distinct genetic liability profiles define clinically relevant patient strata across common diseases.Nature communications · 2024Article
- Integration of a polygenic score into guideline-recommended prediction of cardiovascular disease.European heart journal · 2024Article
- Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis.Circulation research · 2024Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
backgroundThe joint contribution of genetic and environmental exposures to noncommunicable diseases is not well characterized.
objectivesWe modeled the cumulative effects of common risk alleles and their prevalence variations with classical risk factors.
methodsWe analyzed mathematically and statistically numbers and effect sizes of established risk alleles for coronary artery disease (CAD) and other conditions.
resultsIn UK Biobank, risk alleles counts in the lowest (175.4) and highest decile (205.7) of the distribution differed by only 16.9%, which nevertheless increased CAD prevalence 3.4-fold (p < 0.01). Irrespective of the affected gene, a single risk allele multiplied the effects of all others carried by a person, resulting in a 2.9-fold stronger effect size in the top versus the bottom decile (p < 0.01) and an exponential increase in risk (R > 0.94). Classical risk factors shifted effect sizes to the steep upslope of the logarithmic function linking risk allele numbers with CAD prevalence. Similar phenomena were observed in the Estonian Biobank and for risk alleles affecting diabetes mellitus, breast and prostate cancer.
conclusionsAlleles predisposing to common diseases can be carried safely in large numbers, but few additional ones lead to sharp risk increments. Here, we describe exponential functions by which risk alleles combine interchangeably but multiplicatively with each other and with modifiable risk factors to affect prevalence. Our data suggest that the biological systems underlying these diseases are modulated by hundreds of genes but become only fragile when a narrow window of total risk, irrespective of its genetic or environmental origins, has been passed.
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