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性状多基因性的原则性措施和估计

Principled measures and estimates of trait polygenicity.

作者信息

O'Connor Luke J, Sella Guy

机构信息

Department of Biomedical Informatics, Harvard Medical School, Boston, MA.

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.

出版信息

bioRxiv. 2025 Jul 15:2025.07.10.664154. doi: 10.1101/2025.07.10.664154.

Abstract

The 'polygenicity' of traits is often invoked and sometimes quantified in quantitative, statistical, and human genetics. What do we mean by the polygenicity of a trait? We propose a principled definition that encompasses a range of polygenicity measures. We show that these measures satisfy certain mathematical properties, we argue that these properties are sensible if not necessary, and we show that, conversely, measures that satisfy these properties also satisfy our definition. We consider four specific measures in greater detail, describe how they differ and show that three of them can be estimated from GWAS summary statistics using an existing method, Fourier Mixture Regression. We estimate these measures for 36 traits in humans. We find a dearth of traits with polygenicity values that fall within the large gap between Mendelian and highly polygenic traits. We discuss the evolutionary and cellular processes underlying trait polygenicity.

摘要

性状的“多基因性”在数量遗传学、统计遗传学和人类遗传学中经常被提及,有时还会被量化。我们所说的性状多基因性是什么意思呢?我们提出了一个有原则的定义,它涵盖了一系列多基因性度量。我们表明这些度量满足某些数学性质,我们认为这些性质即使不是必要的也是合理的,并且我们还表明,相反地,满足这些性质的度量也符合我们的定义。我们更详细地考虑了四种具体的度量,描述了它们的差异,并表明其中三种可以使用现有的方法——傅里叶混合回归,从全基因组关联研究(GWAS)汇总统计数据中进行估计。我们估计了人类36种性状的这些度量。我们发现多基因性值落在孟德尔性状和高度多基因性状之间巨大差距内的性状很少。我们讨论了性状多基因性背后的进化和细胞过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd8/12338567/42eaddcd7f93/nihpp-2025.07.10.664154v1-f0004.jpg

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