ArticleBiological psychiatry2021
A Comparison of Ten Polygenic Score Methods for Psychiatric Disorders Applied Across Multiple Cohorts.
Article in Biological psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 2 of them syntheses that pooled it.
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Who cites it
120 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Reconstructing SNP allele and genotype frequencies from GWAS summary statistics.Scientific reports · 2022Pooled it
- Polygenic risk for alcohol consumption and multisite chronic pain: Associations with ad lib drinking behavior.Experimental and clinical psychopharmacology · 2023Trial
- Genetic investigation of the association between maternal dietary patterns and offspring ADHD.Molecular psychiatry · 2026Article
- Distinguishing different psychiatric disorders using DDx-PRS.Nature genetics · 2026Article
- Investigating Relationships Between Genetic Risk, Childhood Maltreatment, and Eating Disorders in Women.Biological psychiatry global open science · 2026Article
- A pre-train and fine-tune framework for adaptive boosting of pre-trained polygenic risk scores.Nature communications · 2026Article
- Polygenic Resilience Scores are Associated With Lower Penetrance of Schizophrenia Risk Genes, Protection Against Psychiatric and Medical Disorders, and Enhanced Mental Well-Being and Cognition.Schizophrenia bulletin · 2026Article
- Article
- Recurrent Copy Number Variants and Psychiatric Outcomes in the Context of Polygenic Scores.JAMA psychiatry · 2026Article
- Polygenic scores for risk of pancreatic ductal adenocarcinoma: evaluation of novel and published models.NPJ precision oncology · 2026Article
- Associations between socioeconomic factors and mental symptoms highlight whole-body correlates and pathways.iScience · 2026Article
- Secure bioinformatics: privacy-preserving federated analytics using homomorphic encryption.Bioinformatics (Oxford, England) · 2026Article
- Associations of vegetarianism with circulating lipids across varying genetic capacity: a cross-sectional Polygenic Score-by-Vegetarianism interaction study in UK Biobank.medRxiv : the preprint server for health sciences · 2026Article
- Empirical evaluation of analytic validity of polygenic scores.Genome medicine · 2026Article
- Polygenic scores for psychiatric traits mediate the impact of multigenerational history for depression on offspring psychopathology.Molecular psychiatry · 2026Article
- Cross-Ancestry Polygenic Prediction: Comparing Methods and Assessing Transferability Across Traits.Genetic epidemiology · 2026Article
- Comprehensive benchmarking single and multi ancestry polygenic score methods with the PGS-hub platform.Nature communications · 2026Article
- Improving performance of polygenic risk scores for hypertension across two ancestry groups.PloS one · 2026Article
- Article
60 more citing papers are in PubMed but not listed here.
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16 authors.
Funding
Abstract
backgroundPolygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies. PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in applications to real data sets, which could reflect a number of factors, e.g., phenotype definition or technical factors.
methodsThe Psychiatric Genomics Consortium Working Groups for schizophrenia and major depressive disorder bring together many independently collected case-control cohorts. We used these resources (31,328 schizophrenia cases, 41,191 controls; 248,750 major depressive disorder cases, 563,184 controls) in repeated application of leave-one-cohort-out meta-analyses, each used to calculate and evaluate PGS in the left-out (target) cohort. Ten PGS methods (the baseline PC+T method and 9 methods that model genetic architecture more formally: SBLUP, LDpred2-Inf, LDpred-funct, LDpred2, Lassosum, PRS-CS, PRS-CS-auto, SBayesR, MegaPRS) were compared.
resultsCompared with PC+T, the other 9 methods gave higher prediction statistics, MegaPRS, LDPred2, and SBayesR significantly so, explaining up to 9.2% variance in liability for schizophrenia across 30 target cohorts, an increase of 44%. For major depressive disorder across 26 target cohorts, these statistics were 3.5% and 59%, respectively.
conclusionsAlthough the methods that more formally model genetic architecture have similar performance, MegaPRS, LDpred2, and SBayesR rank highest in most comparisons and are recommended in applications to psychiatric disorders.
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