ArticlePLoS genetics2021
Evaluation of polygenic prediction methodology within a reference-standardized framework.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 4 of them syntheses that pooled it.
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Who cites it
104 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Genome-wide association studies of infant and toddler temperament in European and multi-ancestry populations.Nature human behaviour · 2026Pooled it
- Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling.Nature genetics · 2026Pooled it
- Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry.Nature human behaviour · 2025Pooled it
- Systematic Review: How the Attention-Deficit/Hyperactivity Disorder Polygenic Risk Score Adds to Our Understanding of ADHD and Associated Traits.Journal of the American Academy of Child and Adolescent Psychiatry · 2021Pooled it
- All of Us diversity and scale yield context-dependent improvements in polygenic prediction.Nature genetics · 2026Article
- Evaluation of Sex-Stratified Polygenic Risk Scores for Type 2 Diabetes Mellitus and Glycemic Traits in the Framingham Heart Study.Diabetes & metabolism journal · 2026Article
- Metabolomic ageing across mental and behavioural disorders.BMJ mental health · 2026Article
- Polygenic scores for risk of pancreatic ductal adenocarcinoma: evaluation of novel and published models.NPJ precision oncology · 2026Article
- Metabolomic ageing (MileAge) in mid-life predicts incident vascular, unspecified and all-cause dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Empirical evaluation of analytic validity of polygenic scores.Genome medicine · 2026Article
- Article
- Clinical use of polygenic risk scores: current status, barriers and future directions.Nature reviews. Genetics · 2026Review
- Comprehensive benchmarking single and multi ancestry polygenic score methods with the PGS-hub platform.Nature communications · 2026Article
- Integrating Imaging-Derived Clinical Endotypes with Plasma Proteomics and External Polygenic Risk Scores Enhances Coronary Microvascular Disease Risk Prediction.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2026Article
- Systematic Review and Meta-Analysis: Phenotypic Correlates of the Autism Polygenic Score.JAACAP open · 2025Article
- Polygenic risks and cardiovascular treatment effects in severe mental illness.Psychiatric genetics · 2025Article
- Imputation disparities driven by recent selection and their impact on disease risk estimation in East and Southeast Asian populations.Communications biology · 2025Article
- Statistical construction of calibrated prediction intervals for polygenic score-based phenotype prediction.Nature genetics · 2025Article
- Sparse polygenic risk score inference with the spike-and-slab LASSO.Bioinformatics (Oxford, England) · 2025Article
- Association between hot spring residency and dry eye disease: a crossover gene-environment interaction (GxE) study in Taiwan.Human genomics · 2025Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors.
Funding
Abstract
The predictive utility of polygenic scores is increasing, and many polygenic scoring methods are available, but it is unclear which method performs best. This study evaluates the predictive utility of polygenic scoring methods within a reference-standardized framework, which uses a common set of variants and reference-based estimates of linkage disequilibrium and allele frequencies to construct scores. Eight polygenic score methods were tested: p-value thresholding and clumping (pT+clump), SBLUP, lassosum, LDpred1, LDpred2, PRScs, DBSLMM and SBayesR, evaluating their performance to predict outcomes in UK Biobank and the Twins Early Development Study (TEDS). Strategies to identify optimal p-value thresholds and shrinkage parameters were compared, including 10-fold cross validation, pseudovalidation and infinitesimal models (with no validation sample), and multi-polygenic score elastic net models. LDpred2, lassosum and PRScs performed strongly using 10-fold cross-validation to identify the most predictive p-value threshold or shrinkage parameter, giving a relative improvement of 16-18% over pT+clump in the correlation between observed and predicted outcome values. Using pseudovalidation, the best methods were PRScs, DBSLMM and SBayesR. PRScs pseudovalidation was only 3% worse than the best polygenic score identified by 10-fold cross validation. Elastic net models containing polygenic scores based on a range of parameters consistently improved prediction over any single polygenic score. Within a reference-standardized framework, the best polygenic prediction was achieved using LDpred2, lassosum and PRScs, modeling multiple polygenic scores derived using multiple parameters. This study will help researchers performing polygenic score studies to select the most powerful and predictive analysis methods.
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