ArticleGenetics2025
Characterizing selection on complex traits through conditional frequency spectra.
Article in Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed.
- Genetic architectures of brain-related traits are shaped by strong selective constraints.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Investigations on transferability of polygenic risk scores depending on demography and dominance coefficients.HGG advances · 2026Article
- Buffering of gene dosage response curves for human complex traits.Cell genomics · 2026Article
- 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
- Inference of population demographic history captures differing evolutionary signals based on the number of individuals in the dataset.bioRxiv : the preprint server for biology · 2026Article
- Genetic architectures of brain-related traits are shaped by strong selective constraints.bioRxiv : the preprint server for biology · 2026Article
- Representation in genetic studies affects inference about genetic architecture.bioRxiv : the preprint server for biology · 2026Article
- The effect of long-range linkage disequilibrium on allele-frequency dynamics under stabilizing selection.PLoS genetics · 2026Article
- Farm animal evolution demonstrates hidden molecular basis of human traits.bioRxiv : the preprint server for biology · 2026Article
- Three open questions in polygenic score portability.Nature communications · 2026Article
- Per-allele disease and complex trait effect sizes are predominantly African MAF-dependent in European populations.medRxiv : the preprint server for health sciences · 2026Article
- The genetic architecture and spatiotemporal dynamics of adaptation across human-modified landscapes.The New phytologist · 2026Review
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- Biobanks in GENETICS and G3: tackling the statistical challenges.G3 (Bethesda, Md.) · 2025Article
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Abstract
Natural selection on complex traits is difficult to study in part due to the ascertainment inherent to genome-wide association studies (GWAS). The power to detect a trait-associated variant in GWAS is a function of its frequency and effect size - but for traits under selection, the effect size of a variant determines the strength of selection against it, constraining its frequency. Recognizing the biases inherent to GWAS ascertainment, we propose studying the joint distribution of allele frequencies across populations, conditional on the frequencies in the GWAS cohort. Before considering these conditional frequency spectra, we first characterized the impact of selection and non-equilibrium demography on allele frequency dynamics forwards and backwards in time. We then used these results to understand conditional frequency spectra under realistic human demography. Finally, we investigated empirical conditional frequency spectra for GWAS variants associated with 106 complex traits, finding compelling evidence for either stabilizing or purifying selection. Our results provide insights into polygenic score portability and other properties of variants ascertained with GWAS, highlighting the utility of conditional frequency spectra.
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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 OpenQuestion graph.