西奈山伊坎医学院P. F. O’Reilly小组取得一项新突破。他们提出了复杂性状尾部的独特遗传结构。相关论文发表在2026年5月27日出版的《自然》杂志上。

在这里，课题组人员开发了一种基于多基因风险评分的方法，该方法揭示了74个数量性状的一个或两个尾部普遍偏离共同变异结构。这些观察结果在不同的祖先、群体和重复的测量中得到了重复，并提出了另一种基于家庭的方法。结合从序列数据中识别的罕见变异导致这些偏差的显著减少，这表明大影响的罕见等位基因是性状-尾部结构的关键驱动因素。正向模拟表明，稳定选择可以产生观察到的模式，而模拟繁殖成功为选择的作用提供了经验支持。这些发现表明，尽管复杂性状在总体上是多基因的，但由于选择，它们的尾部具有明显的多基因结构。这对罕见变异的发现以及复杂性状和疾病的预测具有重要意义。

据悉，复杂性状具有高度的多基因性，其遗传能力可以用数百种影响较小的常见变异和影响较大的罕见变异来解释。然而，这种遗传结构如何在性状连续体中变化，以及自然选择在形成这种变化中的作用，一直没有得到充分的探索。

附：英文原文

Title: Distinct genetic architecture in the tails of complex traits

Author: Souaiaia, T., Wu, H. M., Ori, A. P. S., Choi, S. W., Hoggart, C. J., OReilly, P. F.

Issue&Volume: 2026-05-27

Abstract: Complex traits are highly polygenic, with heritability explained by many hundreds of common variants of small effect together with rare variants of large effect1. Yet how this genetic architecture varies along the trait continuum has been underexplored, as has the role of natural selection in shaping this variation. Here we developed an approach based on polygenic risk scores that reveals widespread departures from common-variant architecture in one or both of the tails of 74 quantitative traits. These observations were replicated across ancestries, cohorts and repeated measures and using an alternative family-based approach2. Incorporating rare variants identified from sequence data resulted in marked reductions in these deviations, suggesting that rare alleles of large effect are key drivers of trait-tail architecture. Forward simulations showed that stabilizing selection could generate the observed patterns, whereas modelling reproductive success provided empirical support for the role of selection. These findings show that although complex traits are polygenic in the population at large, they have a distinct and less polygenic architecture in their tails due to selection. This has implications for rare-variant discovery and complex trait and disease prediction.

DOI: 10.1038/s41586-026-10516-5

Source: https://www.nature.com/articles/s41586-026-10516-5