ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2022
Population differentiation of polygenic score predictions under stabilizing selection.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- Effect of population structure and stabilizing selection on quantitative genetic variation.Genetics · 2026Article
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- Dissecting Fluctuating Selection: A Unified Population and Quantitative Genetics Framework.Genome biology and evolution · 2026Article
- Divergent habitat selection across many loci maintains species boundaries during introgression.bioRxiv : the preprint server for biology · 2026Article
- Article
- Observational epidemiological studies can mitigate genetic confounding with a genetic relatedness matrix.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Chromosome-specific drift under stabilizing selection generates polygenic barriers to sex chromosome turnover.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The effect of long-range linkage disequilibrium on allele-frequency dynamics under stabilizing selection.PLoS genetics · 2026Article
- Three open questions in polygenic score portability.Nature communications · 2026Article
- On ARGs, pedigrees, and genetic relatedness matrices.Genetics · 2026Article
- The ChickenGTEx portal: a pan-tissue catalogue of regulatory variants shaping transcriptomic and phenotypic diversity.Nucleic acids research · 2026Article
- Polygenic prediction of human complex traits using ancient DNA.Current opinion in genetics & development · 2025Review
- Predicting the direction of phenotypic difference.Nature communications · 2025Article
- Natural selection acting on complex traits hampers the predictive accuracy of polygenic scores in ancient samples.American journal of human genetics · 2025Article
- Article
- Article
- Interpreting SNP heritability in admixed populations.bioRxiv : the preprint server for biology · 2025Article
- On ARGs, pedigrees, and genetic relatedness matrices.bioRxiv : the preprint server for biology · 2025Article
- Archaic introgression and the distribution of shared variation under stabilizing selection.PLoS genetics · 2025Article
- Fine-scale population structure and widespread conservation of genetic effect sizes between human groups across traits.Nature genetics · 2025Article
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2 authors.
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Abstract
Given the many small-effect loci uncovered by genome-wide association studies (GWAS), polygenic scores have become central to genomic medicine, and have found application in diverse settings including evolutionary studies of adaptation. Despite their promise, polygenic scores have been found to suffer from limited portability across human populations. This at first seems in conflict with the observation that most common genetic variation is shared among populations. We investigate one potential cause of this discrepancy: stabilizing selection on complex traits. Counterintuitively, while stabilizing selection constrains phenotypic evolution, it accelerates the loss and fixation of alleles underlying trait variation within populations (GWAS loci). Thus even when populations share an optimum phenotype, stabilizing selection erodes the variance contributed by their shared GWAS loci, such that predictions from GWAS in one population explain less of the phenotypic variation in another. We develop theory to quantify how stabilizing selection is expected to reduce the prediction accuracy of polygenic scores in populations not represented in GWAS samples. In addition, we find that polygenic scores can substantially overstate average genetic differences of phenotypes among populations. We emphasize stabilizing selection around a common optimum as a useful null model to connect patterns of allele frequency and polygenic score differentiation. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.
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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 Socratic graph.