ArticleEuropean journal of human genetics : EJHG2021
Polygenic risk modeling with latent trait-related genetic components.
Article in European journal of human genetics : EJHG, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- 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
- Inclusion bias affects common variant discovery and replication in a health-system linked biobank.American journal of human genetics · 2026Article
- Identifying chronic obstructive pulmonary disease subtypes using multi-trait genetics.EBioMedicine · 2025Article
- A genome-wide association study of mammographic texture variation.Breast cancer research : BCR · 2022Article
- LARGE-SCALE MULTIVARIATE SPARSE REGRESSION WITH APPLICATIONS TO UK BIOBANK.The annals of applied statistics · 2022Article
- Significant sparse polygenic risk scores across 813 traits in UK Biobank.PLoS genetics · 2022Article
- Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanisms.Neurobiology of disease · 2022Review
- Polygenic Risk Score in African populations: progress and challenges.F1000Research · 2022Review
- Cross-ancestry genome-wide association studies identified heterogeneous loci associated with differences of allele frequency and regulome tagging between participants of European descent and other ancestry groups from the UK Biobank.Human molecular genetics · 2021Article
- Clinical genetics-it's polygenic.European journal of human genetics : EJHG · 2021Article
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6 authors.
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Abstract
Polygenic risk models have led to significant advances in understanding complex diseases and their clinical presentation. While polygenic risk scores (PRS) can effectively predict outcomes, they do not generally account for disease subtypes or pathways which underlie within-trait diversity. Here, we introduce a latent factor model of genetic risk based on components from Decomposition of Genetic Associations (DeGAs), which we call the DeGAs polygenic risk score (dPRS). We compute DeGAs using genetic associations for 977 traits and find that dPRS performs comparably to standard PRS while offering greater interpretability. We show how to decompose an individual's genetic risk for a trait across DeGAs components, with examples for body mass index (BMI) and myocardial infarction (heart attack) in 337,151 white British individuals in the UK Biobank, with replication in a further set of 25,486 non-British white individuals. We find that BMI polygenic risk factorizes into components related to fat-free mass, fat mass, and overall health indicators like physical activity. Most individuals with high dPRS for BMI have strong contributions from both a fat-mass component and a fat-free mass component, whereas a few "outlier" individuals have strong contributions from only one of the two components. Overall, our method enables fine-scale interpretation of the drivers of genetic risk for complex 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.