墨西哥人群中祖先对复杂性状的家族内效应
墨西哥人群中祖先对复杂性状的家族内效应
作者： 小柯机器人 发布时间：2026/9/12 10:12:28
本期文章：《自然》：Online/在线发表
2026年9月9日，英国牛津大学Siqi Wang等科学家在《自然》（Nature）发表研究，利用墨西哥城前瞻性研究（MCPS）的家族数据，揭示了美洲原住民祖先对身高和2型糖尿病的家族内遗传效应。
人类群体在疾病患病率和表型上存在差异，但对于大多数复杂性状而言，这些差异在多大程度上由遗传因素引起仍属未知。比较群体间的表型均值会受到环境差异的混淆，而使用多基因预测因子可能导致有偏推断。对具有遗传混合祖先的人群进行基于家族的分析，能够估计不受祖先–环境相关性混淆的祖先效应。本研究利用墨西哥城前瞻性研究（MCPS）中混合祖先成年人的遗传数据，估计家族内祖先效应。研究人员评估了52,583名无亲缘关系个体及来自17,627个家庭的39,714名亲属的遗传祖先和15种复杂性状。在群体水平上，相对于欧洲祖先，美洲原住民祖先对身高的效应为−1.98个标准差（P < 2 × 10?¹?），对2型糖尿病的自然对数优势比为1.73（95%置信区间，1.54–1.92）。在家族内，美洲原住民祖先对身高的效应为−1.51个标准差（P = 10??），对2型糖尿病的自然对数优势比为5.13（95%置信区间，2.48–7.78）。这些效应得到祖先间性状增加等位基因计数差异以及性状相关位点选择证据的支持。尽管在群体水平上存在显著关联，但研究人员未发现家族内祖先对教育程度或其他性状的效应，这提示存在环境原因或混杂。总体而言，本研究提供了一种研究祖先间遗传效应的实验设计，并在墨西哥城一个遗传多样性群体中识别出身高、2型糖尿病和代谢性状的显著祖先差异。
附：英文原文
Title: Within-family effect of ancestry on complex traits in a Mexican population
Author: Wang, Siqi, Berumen, Jaime, Vergara-Lope, Alejandra, Baca, Paulina, Barrera, Elizabeth, Rivas, Fernando, Aguilar-Ramirez, Diego, Collins, Rory, Emberson, Jonathan R., Hill, Michael, Goddard, Michael E., Yengo, Loic, Young, Alexander Strudwick, Alegre-Daz, Jesus, Kuri-Morales, Pablo, Tapia-Conyer, Roberto, Torres, Jason M., Visscher, Peter M.
Issue&Volume: 2026-09-09
Abstract: Human populations differ in disease prevalence and phenotypes, but the extent to which differences are caused by genetic factors is unknown for most complex traits. Comparing phenotypic means across populations is confounded by environmental differences and using polygenic predictors can lead to biased inference1,2. Family-based analyses of people of genetically admixed ancestry enable estimation of ancestry effects unconfounded by ancestry–environment correlations. Here we leverage genetic data from admixed adults in the Mexico City Prospective Study3,4 to estimate within-family ancestry effects5. We assessed genetic ancestry and 15 complex traits in 52,583 unrelated people and 39,714 relatives from 17,627 families. At the population level, relative to European ancestry, the effect of Indigenous American ancestry was 1.98 s.d. (P<2×1016) for height and a natural log odds ratio of 1.73 (95% confidence interval, 1.54–1.92) for type2 diabetes. Within families, the effect of Indigenous American ancestry was 1.51s.d. (P=108) for height and natural log odds ratio of 5.13 (95% confidence interval, 2.48–7.78) for type 2 diabetes. These effects are supported by between-ancestry differences in trait-increasing allele counts and evidence of selection at trait-associated loci. We found no within-family ancestry effect on educational attainment or other traits despite significant associations at the population level, implying environmental causes or confounding. Overall, this study provides an experimental design to study between-ancestry genetic effects and identifies significant ancestry differences for height, type 2 diabetes and metabolic traits in a genetically diverse population from Mexico City.
DOI: 10.1038/s41586-026-11039-9
Source: https://www.nature.com/articles/s41586-026-11039-9