多样化基因组,共享健康:来自卫生系统生物库的见解
Roni Haas1,2,3,4, Michael P Margolis1,5,6, Angela Wei1,7,8,9
1Department of Human Genetics, University of California, Los Angeles, USA.
medRxiv : the preprint server for health sciences
|June 30, 2025
概括
多样化的生物库对于精准医学至关重要,但往往缺乏祖先的多样性. 这项研究使用了多样化的生物库来识别新的遗传关联,并改善各种人群的疾病预测.
科学领域:
- 基因组学和精准医学精准医学
- 人口遗传学 人口遗传学
- 健康差异 在健康上的差异
背景情况:
- 精准医学依赖于基因分析和电子健康记录,但有限的祖先多样性阻碍了发现和概括性.
- 医院生物库往往缺乏非欧洲人口的代表性,在了解疾病患病率和遗传风险方面造成差距.
研究的目的:
- 利用多样化的生物库 (UCLA ATLAS社区健康倡议) 来调查不同祖先群体的疾病流行率和遗传风险.
- 为了确定新的遗传关联,并评估跨不同祖先的多基因分数的表现.
- 解决策划的临床变异中的偏见,并在代表性不足的人群中发现新的基因疾病关联.
主要方法:
- 分析了来自93,937个人的临床和遗传数据,包括61,797名参与者的全外因子测序 (WES).
- 对五大洲和36个细度祖先群体的疾病患病率和遗传风险的检查.
- 利用计算预测的有害变异来减轻在精心策划的临床变异数据库中的偏差.
主要成果:
- 发现了新的关联,包括*STARD7*与墨西哥裔美国人的喘和*FN3K*与肠道脱糖酶缺乏症.
- 多基因分数 (PGS) 显示,非欧洲人口中常见疾病的预测能力下降.
- 确定了新的基因疾病关联,例如*EXOC1L*与东亚人的血糖,以及*PTPRU*作为半氨酸减肥效应的调节器.
结论:
- 生物库的祖先多样性对于推进精确健康和确保跨人群公平发现至关重要.
- 解决遗传数据库中的偏见,并纳入各种数据对于准确的疾病预测和治疗至关重要.
- 这项研究强调了包容性研究的必要性,以充分实现精准医学对所有人的潜力.
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