小柯机器人

美国加州大学洛杉矶分校Bogdan Pasaniuc和Kangcheng Hou共同合作，近期取得重要工作进展。他们研究发现混合血统个体中不同大陆血统的常见变异对复杂性状的因果影响相似。相关研究成果2023年3月20日在线发表于《自然—遗传学》杂志上。

据介绍，混合血统的个体（例如，非裔美国人）继承了起源于多个大陆祖先种群嵌合的基因片段。这为研究同一群体中不同祖先的遗传效应对性状的相似性影响提供了独特的机会。

研究人员介绍了一种方法来估计因果遗传效应 （r_admix）在当地血统之间的相关性，并分析了非洲-欧洲混血个体（N=53001）的38个复杂特征，以观察到非常高的相关性（荟萃分析 r_admix=0.95，95%可信区间0.93–0.97），远高于大陆血统之间因果关系的相关性。研究人员使用基于回归的方法从边缘全基因组关联研究汇总统计数据中再现了这一结果。研究人员还报告了现实场景，其中基于回归的方法由于因果效应和多基因性的特定血统标记而产生夸大的血统异质性。

总之，这一研究结果促进了遗传分析，假设血统因果效应的异质性最小，这对将血统多样化的个体纳入研究具有重要意义。

附：英文原文

Title: Causal effects on complex traits are similar for common variants across segments of different continental ancestries within admixed individuals

Author: Hou, Kangcheng, Ding, Yi, Xu, Ziqi, Wu, Yue, Bhattacharya, Arjun, Mester, Rachel, Belbin, Gillian M., Buyske, Steve, Conti, David V., Darst, Burcu F., Fornage, Myriam, Gignoux, Chris, Guo, Xiuqing, Haiman, Christopher, Kenny, Eimear E., Kim, Michelle, Kooperberg, Charles, Lange, Leslie, Manichaikul, Ani, North, Kari E., Peters, Ulrike, Rasmussen-Torvik, Laura J., Rich, Stephen S., Rotter, Jerome I., Wheeler, Heather E., Wojcik, Genevieve L., Zhou, Ying, Sankararaman, Sriram, Pasaniuc, Bogdan

Issue&Volume: 2023-03-20

Abstract: Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the unique opportunity of investigating the similarity of genetic effects on traits across ancestries within the same population. Here we introduce an approach to estimate correlation of causal genetic effects (radmix) across local ancestries and analyze 38 complex traits in African-European admixed individuals (N=53,001) to observe very high correlations (meta-analysis radmix=0.95, 95% credible interval 0.93–0.97), much higher than correlation of causal effects across continental ancestries. We replicate our results using regression-based methods from marginal genome-wide association study summary statistics. We also report realistic scenarios where regression-based methods yield inflated heterogeneity-by-ancestry due to ancestry-specific tagging of causal effects, and/or polygenicity. Our results motivate genetic analyses that assume minimal heterogeneity in causal effects by ancestry, with implications for the inclusion of ancestry-diverse individuals in studies.

DOI: 10.1038/s41588-023-01338-6

Source: https://www.nature.com/articles/s41588-023-01338-6

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex