ArticleGenome medicine2010
Multi-locus models of genetic risk of disease.
Article in Genome medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Neuropsychiatry genetics in Africa.Nature communications · 2026Review
- Polygenic backgrounds influence phenotypic consequences of variants in cells, individuals, and populations.Cell genomics · 2026Review
- Polygenic risk scores: Navigating the future of precision medicine through economic, ethical, and scientific advancements.iScience · 2026Review
- Mutation-selection-drift balance models of complex diseases.Genetics · 2025Article
- Exposure accumulation drives age-dependent disease architectures and polygenic risk scores.medRxiv : the preprint server for health sciences · 2025Article
- Mutation-selection-drift balance models of complex diseases.bioRxiv : the preprint server for biology · 2025Article
- Evaluation of Machine Learning and Traditional Statistical Models to Assess the Value of Stroke Genetic Liability for Prediction of Risk of Stroke Within the UK Biobank.Healthcare (Basel, Switzerland) · 2025Article
- Genotype × environment interactions in gene regulation and complex traits.Nature genetics · 2024Review
- A perspective on genetic and polygenic risk scores-advances and limitations and overview of associated tools.Briefings in bioinformatics · 2024Review
- Implementation of type 1 diabetes genetic risk screening in children in diverse communities: the Virginia PrIMeD project.Genome medicine · 2024Article
- Whole Exome Sequencing of Hemiplegic Migraine Patients Shows an Increased Burden of Missense Variants in CACNA1H and CACNA1I Genes.Molecular neurobiology · 2023Article
- Genetic and modifiable risk factors combine multiplicatively in common disease.Clinical research in cardiology : official journal of the German Cardiac Society · 2023Article
- Canalization of the Polygenic Risk for Common Diseases and Traits in the UK Biobank Cohort.Molecular biology and evolution · 2022Article
- Article
- Polymorphism in the 3'-UTR of LIF but Not in the ATF6B Gene Associates with Schizophrenia Susceptibility: a Case-Control Study and In Silico Analyses.Journal of molecular neuroscience : MN · 2020Article
- Article
- Leveraging correlations between variants in polygenic risk scores to detect heterogeneity in GWAS cohorts.PLoS genetics · 2020Article
- Population genetic simulation study of power in association testing across genetic architectures and study designs.Genetic epidemiology · 2020Article
- Genetic Risk Scores.Current protocols in human genetics · 2019Review
- Validity of polygenic risk scores: are we measuring what we think we are?Human molecular genetics · 2019Review
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEvidence for genetic contribution to complex diseases is described by recurrence risks to relatives of diseased individuals. Genome-wide association studies allow a description of the genetics of the same diseases in terms of risk loci, their effects and allele frequencies. To reconcile the two descriptions requires a model of how risks from individual loci combine to determine an individual's overall risk.
methodsWe derive predictions of risk to relatives from risks at individual loci under a number of models and compare them with published data on disease risk.
resultsThe model in which risks are multiplicative on the risk scale implies equality between the recurrence risk to monozygotic twins and the square of the recurrence risk to sibs, a relationship often not observed, especially for low prevalence diseases. We show that this theoretical equality is achieved by allowing impossible probabilities of disease. Other models, in which probabilities of disease are constrained to a maximum of one, generate results more consistent with empirical estimates for a range of diseases.
conclusionsThe unconstrained multiplicative model, often used in theoretical studies because of its mathematical tractability, is not a realistic model. We find three models, the constrained multiplicative, Odds (or Logit) and Probit (or liability threshold) models, all fit the data on risk to relatives. Currently, in practice it would be difficult to differentiate between these models, but this may become possible if genetic variants that explain the majority of the genetic variance are identified.
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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.