Simple scaling laws control the genetic architectures of human complex traits.
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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,
SUBMITTER: Simons YB
PROVIDER: S-EPMC12517483 | biostudies-literature | 2025 Oct
REPOSITORIES: biostudies-literature
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