在百万退伍军人计划中模拟祖先多样性的纵向变化
Frank R Wendt1,2, Gita A Pathak1,2, Jacqueline Vahey3,4
1Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Human genomics
|June 2, 2023
概括
百万退伍军人计划 (MVP) 显示,随着时间的推移,祖先的变化影响了全基因组关联研究 (GWAS). 一种精细的祖先分配方法有效地减少了GWAS中混的人口分层.
科学领域:
- 遗传学 是一个遗传学.
- 人口遗传学 人口遗传学
- 基因组流行病学 基因组流行病学
背景情况:
- 百万退伍军人计划 (MVP) 队列涵盖了美国100年的历史,反映了重大的社会和人口变化.
- 在MVP中了解人口多样性的纵向变化对于遗传研究至关重要.
- 评估这些人口变化如何影响全基因组关联研究 (GWAS) 对于准确的遗传见解至关重要.
研究的目的:
- 在百万退伍军人计划 (MVP) 队列中对祖先多样性的纵向变化进行表征.
- 评估两种不同的策略来推断基因定义的祖先群体.
- 为了比较这些策略在控制全基因组关联研究 (GWAS) 中人口分层的有效性.
主要方法:
- MVP参与者被分为五个出生队伍,从1943年到1953年.
- 祖先群体使用协调祖先和种族/种族 (HARE) 和随机森林集群方法定义,使用1000个基因组项目和人类基因组多样性项目 (1kGP+HGDP) 参考面板.
- 对身高进行了全基因组关联研究 (GWAS),并使用链接不平衡得分回归评估了人口分层.
主要成果:
- 在出生队伍中观察到祖先多样性的显著趋势,HARE分配的欧洲人,非洲人和西班牙裔的欧洲祖先比例有显著的变化.
- 随着时间的推移,HARE分配的东亚人显示出越来越多的欧洲血统.
- 使用HARE分配的全基因组关联研究 (GWAS) 显示出由于人口分层而导致的流行基因组通胀,该通胀因1kGP+HGDP的祖先分配而显著减少.
结论:
- 该研究描述了MVP队伍不断变化的祖先景观.
- 它表明,精细的祖先推断方法,如1kGP+HGDP方法,可以有效地减轻GWAS中的人口分层.
- 这些发现对于提高不同人群中遗传关联研究的准确性和可靠性至关重要.
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