ArticleProceedings of the National Academy of Sciences of the United States of America2021
A model and test for coordinated polygenic epistasis in complex traits.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Context-specific genetic effects inform endotypes and treatment in asthma.The Journal of allergy and clinical immunology · 2026Article
- Dissecting the polygenic architecture of psychopathology via singular value decomposition of eight psychiatric genome-wide association studies and evaluation of component-based polygenic scores.General psychiatry · 2026Article
- The geometry of G × E: How scaling and endogenous treatment effects shape interaction direction.PLoS genetics · 2026Article
- Choice of phenotype scale is critical in biobank-based G×E tests.bioRxiv : the preprint server for biology · 2026Article
- A biobank-scale test of marginal epistasis reveals genome-wide signals of polygenic interaction effects.Nature genetics · 2025Article
- Epistatic contributions to human traits via transcription factor mechanisms.medRxiv : the preprint server for health sciences · 2025Article
- Learning sequence-function relationships with scalable, interpretable Gaussian processes.bioRxiv : the preprint server for biology · 2025Article
- Genetic risk effects on psychiatric disorders act in sets.medRxiv : the preprint server for health sciences · 2025Article
- Beyond predictive RAmerican journal of human genetics · 2025Article
- Deep learning-based polygenic scores enhance generalizability of psychiatric disorders prediction.medRxiv : the preprint server for health sciences · 2025Article
- Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens.Human genomics · 2024Review
- Genetic Prediction Modeling in Large Cohort Studies via Boosting Targeted Loss Functions.Statistics in medicine · 2024Article
- Understanding genetic variants in context.eLife · 2024Article
- A scalable adaptive quadratic kernel method for interpretable epistasis analysis in complex traits.Genome research · 2024Article
- Cluster effect for SNP-SNP interaction pairs for predicting complex traits.Scientific reports · 2024Article
- Factorizing polygenic epistasis improves prediction and uncovers biological pathways in complex traits.American journal of human genetics · 2023Article
- Exploring pathway interactions to detect molecular mechanisms of disease: 22q11.2 deletion syndrome.Orphanet journal of rare diseases · 2023Article
- Applying an evolutionary mismatch framework to understand disease susceptibility.PLoS biology · 2023Article
- Leveraging the genetic correlation between traits improves the detection of epistasis in genome-wide association studies.G3 (Bethesda, Md.) · 2023Article
- Improving Genetic Association Studies with a Novel Methodology that Unveils the Hidden Complexity of All-Cause Heart Failure.medRxiv : the preprint server for health sciences · 2023Article
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6 authors at 3 institutions in 1 country.
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Abstract
Interactions between genetic variants-epistasis-is pervasive in model systems and can profoundly impact evolutionary adaption, population disease dynamics, genetic mapping, and precision medicine efforts. In this work, we develop a model for structured polygenic epistasis, called coordinated epistasis (CE), and prove that several recent theories of genetic architecture fall under the formal umbrella of CE. Unlike standard epistasis models that assume epistasis and main effects are independent, CE captures systematic correlations between epistasis and main effects that result from pathway-level epistasis, on balance skewing the penetrance of genetic effects. To test for the existence of CE, we propose the even-odd (EO) test and prove it is calibrated in a range of realistic biological models. Applying the EO test in the UK Biobank, we find evidence of CE in 18 of 26 traits spanning disease, anthropometric, and blood categories. Finally, we extend the EO test to tissue-specific enrichment and identify several plausible tissue-trait pairs. Overall, CE is a dimension of genetic architecture that can capture structured, systemic forms of epistasis in complex human traits.
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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.