通过对遗传学,环境和社会文化因素进行适当的建模,提高GWAS在代表性不足的群体中的表现
Chelsea C Cataldo-Ramirez1,2, Meng Lin3,4, Aislinn Mcmahon1
1Department of Anthropology, University of California Davis, Davis, CA, 95616, USA.
bioRxiv : the preprint server for biology
|November 18, 2024
概括
这项研究通过改善英国生物银行中南亚祖先的代表性来加强遗传研究. 将环境因素纳入全基因组关联研究 (GWAS) 显著提高了多基因分数 (PGS) 开发和预测准确性.
科学领域:
- 遗传学和生物信息学
- 人口遗传学 人口遗传学
- 生物统计学 生物统计学
背景情况:
- 全基因组关联研究 (GWAS) 和多基因评分 (PGS) 的发展受到欧洲祖先在生物库中的过度代表性的限制.
- 非欧洲数据,特别是来自南亚人口的数据,未得到充分利用,阻碍了公平的遗传发现.
研究的目的:
- 增强英国生物库 (UKB) 中非欧洲参与者数据的实用性,用于基因分析.
- 增加在UKB的南亚队伍的样本规模和强度.
- 通过纳入环境共变量来提高GWAS和PGS开发的性能.
主要方法:
- UKB参与者鉴定为孟加拉国人,印度人,巴基斯坦人",白人和亚洲人" (WA) 和"任何其他亚洲人" (AOA) 的特征遗传亲和关系.
- 利用受过基因结构和自我认同的种族训练的支持矢量机器 (SVM) 来重新分配1853名AOA和WA参与者.
- 实施了严格的共变量选择程序,将环境因素纳入高度GWAS,比较GWASnull和GWASenv模型.
主要成果:
- 成功增加了1381名参与者的UKB南亚群体样本大小.
- 从环境调整后的GWAS中,多基因评分 (PGS) 的表现显示出与使用十倍大数据集 (R2=0.026) 的模型可比的预测 (R2=0.021).
- 将7-8个环境共变量纳入其中,使得仅仅由PGS解释的差异翻了一番.
结论:
- 利用模两可的种族代码和祖先匹配的归算面板可以提高GWAS的性能.
- 将环境共变量纳入GWAS显著提高了多基因得分预测准确度.
- 这种方法通过改善各种祖先数据的表示性和实用性来使遗传研究民主化.
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