ReviewHuman molecular genetics2019
Validity of polygenic risk scores: are we measuring what we think we are?
Review in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Interactions between Polygenic Risk of Obesity and Dietary Factors on Anthropometric Outcomes: A Systematic Review and Meta-Analysis of Observational Studies.The Journal of nutrition · 2024Pooled it
- Glaucoma Genetic Risk Scores in the Million Veteran Program.Ophthalmology · 2022Pooled it
- Associations of osteoprotegerin (OPG) TNFRSF11B gene polymorphisms with risk of fractures in older adult populations: meta-analysis of genetic and genome-wide association studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Pooled it
- Pooled it
- Urate-Related Genetic Risk Modulates the Anti-Aging Effects of Exogenous Nucleotides: Multi-Omics Evidence From Older Adults.Aging cell · 2026Trial
- Exploring the use of machine and deep learning in genome-wide association studies: a comprehensive review.BioData mining · 2026Review
- Within-sibling attenuation of polygenic risk score accuracy: investigating the effects of principal component analysis, LD score regression, and mixed model association in the UK Biobank.Human genetics · 2026Article
- Can Polygenic Risk Scores for Metabolic Syndrome Contribute to Long-Term Syndrome Development in First-Episode Psychosis Patients? A Naturalistic 21-Year Follow-Up Study.Schizophrenia bulletin · 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
- Genetic analysis of neurodegenerative diseases.The Journal of clinical investigation · 2026Review
- Polygenic scores for executive functioning as predictors of performance improvements after repeated testing in major psychiatric disorders.Scientific reports · 2026Article
- Evaluating the impact of family history and polygenic risk scores on cardiometabolic disease risk.BMC medicine · 2026Article
- Evaluating genetic-based disease prediction approaches through simulation.Human genetics · 2026Article
- Using machine learning to predict and analyze complex trait diseases: Lessons from a simple abstract model.PloS one · 2026Article
- Genetic variation in the glucagon-like peptide-1 receptor protein encoding region is associated with higher heart rate variability, but not with neurodegeneration of the brain, retina, and peripheral nerves: The Maastricht study.Cardiovascular diabetology · 2025Article
- Improvement of polygenic modeling of blood pressure traits using lifestyle information in the UK Biobank.Genetics · 2025Article
- Navigating the Future of Polygenic Risk Scores: Insights from Child and Adolescent Psychiatrists.Child psychiatry and human development · 2025Article
- Review
- Genetic analysis of selection bias in a natural experiment: Investigating in-utero famine effects on elevated body mass index in the Dutch Hunger Winter Families Study.American journal of epidemiology · 2024Article
- A combination of red and processed meat intake and polygenic risk score influences the incidence of hyperuricemia in middle-aged Korean adults.Nutrition research and practice · 2024Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polygenic risk scores (PRSs) have become the standard for quantifying genetic liability in the prediction of disease risks. PRSs are generally constructed as weighted sum scores of risk alleles using effect sizes from genome-wide association studies as their weights. The construction of PRSs is being improved with more appropriate selection of independent single-nucleotide polymorphisms (SNPs) and optimized estimation of their weights but is rarely reflected upon from a theoretical perspective, focusing on the validity of the risk score. Borrowing from psychometrics, this paper discusses the validity of PRSs and introduces the three main types of validity that are considered in the evaluation of tests and measurements: construct, content, and criterion validity. This introduction is followed by a discussion of three topics that challenge the validity of PRS, namely, their claimed independence of clinical risk factors, the consequences of relaxing SNP inclusion thresholds and the selection of SNP weights. This discussion of the validity of PRS reminds us that we need to keep questioning if weighted sums of risk alleles are measuring what we think they are in the various scenarios in which PRSs are used and that we need to keep exploring alternative modeling strategies that might better reflect the underlying biological pathways.
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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.