ArticlePLoS biology2025
Simple scaling laws control the genetic architectures of human complex traits.
Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed.
- Effect of population structure and stabilizing selection on quantitative genetic variation.Genetics · 2026Article
- Maintenance of quantitative genetic variation in regions of restricted recombination via associative overdominance.bioRxiv : the preprint server for biology · 2026Article
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- 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
- Polygenic and monogenic adaptation drive evolutionary rescue at different magnitudes of environmental change.The Journal of heredity · 2026Article
- Allele frequencies at recessive disease genes are mainly determined by pleiotropic effects in heterozygotes.Genetics · 2026Article
- Correlations between causal effect sizes of proximal SNPs vary with functional annotations and implicate stabilizing selection.Nature genetics · 2026Article
- Massively parallel characterization and predictive modelling of neuronal regulatory variation.bioRxiv : the preprint server for biology · 2026Article
- Buffering of gene dosage response curves for human complex traits.Cell genomics · 2026Article
- Evolution of quantitative traits with background selection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Principled measures and estimates of trait polygenicity.American journal of human genetics · 2026Article
- Causal inference clarifies the roles of background selection and mutation rate variation in shaping human genetic diversity.bioRxiv : the preprint server for biology · 2026Article
- Pathway-Level Reorganization of Genetic Signals Associated with Low Bone Mineral Density Across the Menopausal Transition.International journal of molecular sciences · 2026Article
- Background selection in recombining genomes and its consequences for the maintenance of variation in complex traits.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Parameterizing the genetic architecture under stabilizing selection.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
- Quantitative system drift.Proceedings of the National Academy of Sciences of the United States of America · 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
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6 authors.
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Abstract
Genome-wide association studies have revealed that the genetic architectures of complex traits vary widely, including in terms of the numbers, effect sizes, and allele frequencies of significant hits. However, at present we lack a principled way of understanding the similarities and differences among traits. Here, we describe a probabilistic model that combines the effects of mutation, drift, and stabilizing selection at individual sites with a genome-scale model of phenotypic variation. In this model, the architecture of a trait arises from the distribution of selection coefficients of mutations and from two scaling parameters. We fit this model for 95 highly polygenic quantitative traits of different kinds from the UK Biobank. Notably, we infer that all these traits have fairly similar, though not identical, distributions of selection coefficients. This similarity suggests that differences in architectures of highly polygenic traits arise mainly from the two scaling parameters: the mutational target size and heritability per site, which vary by orders of magnitude among traits. When these two scale factors are accounted for, we find that the architectures of all 95 traits are very similar.
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