Expanded table of outlier SNPs.

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.全基因组关联研究（Genome-wide association studies）已揭示，复杂性状的遗传架构差异显著，具体体现在显著关联位点的数量、效应大小以及等位基因频率等维度。然而目前学界尚缺乏一套严谨的方法，以解析不同性状间的共性与差异。本文提出一款概率模型，该模型将单个位点上的突变、遗传漂变与稳定选择效应，与表型变异的全基因组尺度模型相结合。在该模型中，某一性状的遗传架构由突变的选择系数分布，以及两个缩放参数共同决定。我们针对英国生物银行（UK Biobank）中95种不同类型的高度多基因数量性状拟合了该模型。值得注意的是，我们推断所有这些性状的选择系数分布虽不完全一致，但整体较为相似。这一相似性表明，高度多基因性状的架构差异主要源自两个缩放参数：突变靶标大小与单位位点遗传力，这类参数在不同性状间的差异可达数个数量级。当纳入这两个缩放因子后，我们发现95种性状的遗传架构均呈现高度相似性。