ArticleAmerican journal of human genetics2021
Negative selection on complex traits limits phenotype prediction accuracy between populations.
Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
42 citing papers in PubMed.
- Genetic basis of Asian diabetes.Journal of diabetes investigation · 2026Review
- Investigations on transferability of polygenic risk scores depending on demography and dominance coefficients.HGG advances · 2026Article
- Article
- The effect of long-range linkage disequilibrium on allele-frequency dynamics under stabilizing selection.PLoS genetics · 2026Article
- Cross-Ancestry Polygenic Prediction: Comparing Methods and Assessing Transferability Across Traits.Genetic epidemiology · 2026Article
- Three open questions in polygenic score portability.Nature communications · 2026Article
- On ARGs, pedigrees, and genetic relatedness matrices.Genetics · 2026Article
- Determining the driving factors shaping genetic architecture of complex traits in recently admixed populations.bioRxiv : the preprint server for biology · 2025Article
- Inference of complex demographic history using composite likelihood based on whole-genome genealogies.bioRxiv : the preprint server for biology · 2025Article
- SimHumanity: Using SLiM 5.0 to run whole-genome simulations of human evolution.bioRxiv : the preprint server for biology · 2025Article
- Natural selection acting on complex traits hampers the predictive accuracy of polygenic scores in ancient samples.American journal of human genetics · 2025Article
- Study design and the sampling of deleterious rare variants in biobank-scale datasets.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Parameter Scaling in Population Genetics Simulations may Introduce Unintended Background Selection: Considerations for Scaled Simulation Design.Genome biology and evolution · 2025Article
- Article
- On ARGs, pedigrees, and genetic relatedness matrices.bioRxiv : the preprint server for biology · 2025Article
- Allele frequency impacts the cross-ancestry portability of gene expression prediction in lymphoblastoid cell lines.American journal of human genetics · 2024Article
- Population Heterogeneity and Selection of Coronary Artery Disease Polygenic Scores.Journal of personalized medicine · 2024Article
- Natural selection acting on complex traits hampers the predictive accuracy of polygenic scores in ancient samples.bioRxiv : the preprint server for biology · 2024Article
- Heritability of complex traits in sub-populations experiencing bottlenecks and growth.Journal of human genetics · 2024Article
- Conditional frequency spectra as a tool for studying selection on complex traits in biobanks.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Phenotype prediction is a key goal for medical genetics. Unfortunately, most genome-wide association studies are done in European populations, which reduces the accuracy of predictions via polygenic scores in non-European populations. Here, we use population genetic models to show that human demographic history and negative selection on complex traits can result in population-specific genetic architectures. For traits where alleles with the largest effect on the trait are under the strongest negative selection, approximately half of the heritability can be accounted for by variants in Europe that are absent from Africa, leading to poor performance in phenotype prediction across these populations. Further, under such a model, individuals in the tails of the genetic risk distribution may not be identified via polygenic scores generated in another population. We empirically test these predictions by building a model to stratify heritability between European-specific and shared variants and applied it to 37 traits and diseases in the UK Biobank. Across these phenotypes, ∼30% of the heritability comes from European-specific variants. We conclude that genetic association studies need to include more diverse populations to enable the utility of phenotype prediction in all populations.
Indexed as
Identifiers
What OpenQuestion holds
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.