遗传多样性推动了烟草和酒精使用的基因发现
Gretchen R B Saunders1, Xingyan Wang2, Fang Chen2
1Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Nature
|December 8, 2022
概括
这项研究分析了340万人的遗传数据, 增加多样性改善了发现,但多基因风险得分需要多样化的数据来跨越祖先.
科学领域:
- 遗传学
- 行为科学
- 公共卫生
背景情况:
- 烟草和酒精使用是与全球死亡率相关的遗传行为.
- 之前的遗传学研究主要集中在欧洲的祖先,限制了普遍性.
- 了解这些行为的遗传基础对于公共卫生干预至关重要.
研究的目的:
- 在全球不同祖先中识别与烟草和酒精使用相关的基因组位置.
- 通过全转录组关联研究来研究这些位点的功能影响.
- 评估多基因风险评分的遗传结构和预测实用性.
主要方法:
- 从四个主要的全球祖先 (21%非欧洲) 中获取了340万个人的遗传数据.
- 采用全基因组关联研究 (GWAS) 进行发现和精细映射.
- 进行了祖先意识的全转录组关联研究 (TWAS) 进行功能推断.
主要成果:
- 增加样本大小和遗传多样性提高了相关基因组位点的识别和精细绘制.
- 发现烟草和酒精使用的2,143个位点和3,823个相关变体.
- 大多数变种在祖先之间显示一致的效果大小,但多基因风险得分在不同祖先群体中表现不佳.
结论:
- 在研究中扩大遗传多样性可以提高与物质使用行为相关的变体的发现.
- 目前的多基因风险评分并不适用于所有祖先,这凸显了对更具包容性的遗传研究的需求.
- 未来的研究必须优先考虑不同的样本大小,以便从多基因预测中获得公平的利益.
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