School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia.
IHRC-Georgia Tech Applied Bioinformatics Laboratory, Atlanta, Georgia.
Genome Biol Evol. 2020 Sep 1;12(9):1516-1527. doi: 10.1093/gbe/evaa154.
Genome-wide association studies have uncovered thousands of genetic variants that are associated with a wide variety of human traits. Knowledge of how trait-associated variants are distributed within and between populations can provide insight into the genetic basis of group-specific phenotypic differences, particularly for health-related traits. We analyzed the genetic divergence levels for 1) individual trait-associated variants and 2) collections of variants that function together to encode polygenic traits, between two neighboring populations in Colombia that have distinct demographic profiles: Antioquia (Mestizo) and Chocó (Afro-Colombian). Genetic ancestry analysis showed 62% European, 32% Native American, and 6% African ancestry for Antioquia compared with 76% African, 10% European, and 14% Native American ancestry for Chocó, consistent with demography and previous results. Ancestry differences can confound cross-population comparison of polygenic risk scores (PRS); however, we did not find any systematic bias in PRS distributions for the two populations studied here, and population-specific differences in PRS were, for the most part, small and symmetrically distributed around zero. Both genetic differentiation at individual trait-associated single nucleotide polymorphisms and population-specific PRS differences between Antioquia and Chocó largely reflected anthropometric phenotypic differences that can be readily observed between the populations along with reported disease prevalence differences. Cases where population-specific differences in genetic risk did not align with observed trait (disease) prevalence point to the importance of environmental contributions to phenotypic variance, for both infectious and complex, common disease. The results reported here are distributed via a web-based platform for searching trait-associated variants and PRS divergence levels at http://map.chocogen.com (last accessed August 12, 2020).
全基因组关联研究发现了数千种与人类多种特征相关的遗传变异。了解与特征相关的变异在人群内和人群间的分布情况，可以深入了解群体特异性表型差异的遗传基础，尤其是与健康相关的特征。我们分析了哥伦比亚两个相邻人群（安蒂奥基亚[梅斯蒂索]和乔科[非裔哥伦比亚]）之间的 1）个体特征相关变异和 2）共同作用编码多基因特征的变异集合的遗传分化水平。遗传祖先分析显示，与乔科相比，安蒂奥基亚有 62%的欧洲人、32%的美洲原住民和 6%的非洲人，而乔科有 76%的非洲人、10%的欧洲人和 14%的美洲原住民，这与人口统计学和以前的结果一致。遗传差异会混淆多基因风险评分（PRS）在不同人群间的比较；然而，我们没有发现这两个研究人群的 PRS 分布存在任何系统偏差，而且 PRS 的人群特异性差异在很大程度上是小的且对称分布在零周围。安蒂奥基亚和乔科之间个体特征相关单核苷酸多态性的遗传分化和人群特异性 PRS 差异，在很大程度上反映了人群之间可以直接观察到的人体测量表型差异，以及报告的疾病流行率差异。在遗传风险的人群特异性差异与观察到的特征（疾病）流行率不一致的情况下，这表明环境对表型变异的贡献很重要，包括传染病和复杂的常见疾病。报告的结果通过一个基于网络的平台进行分发，用于搜索与特征相关的变异和 PRS 分化水平，网址是 http://map.chocogen.com（最后访问时间：2020 年 8 月 12 日）。
