在不同祖先群体中确定了大麻使用障碍的融合途径
medRxiv : the preprint server for health sciences
|April 1, 2025
概括
关于大麻使用障碍 (CUD) 的遗传研究揭示了欧洲裔美国人,美洲印第安人和墨西哥裔美国人的独特途径. 罕见的变异有助于CUD的严重程度,突出了对多样化的人口研究的需要.
科学领域:
- 遗传学 是一个遗传学.
- 精神病学是一个精神病学.
- 人口健康 人口健康
背景情况:
- 大麻使用障碍 (CUD) 的患病率在美国各族群之间有很大差异.
- 全基因组关联研究 (GWAS) 主要在欧洲血统的人群中发现了CUD位点.
- 罕见和低频率的功能变异可能解释在未经研究的群体中对CUD的遗传贡献.
研究的目的:
- 调查罕见和低频功能变异在三种不同人群中CUD严重性中的作用:欧洲裔美国人 (EA),美洲印第安人 (AI) 和墨西哥裔美国人 (MA).
- 在这些不同的种族群体中确定与CUD严重程度相关的特定基因和生物途径.
主要方法:
- 关联分析侧重于基因和生物通路内的罕见和低频功能变异.
- 研究了三个群体:EA,AI和MA.
- 分析了CUD严重程度作为主要的表型.
主要成果:
- 在AI中确定了10个显著的位置,以及与CUD严重程度相关的MA中的*ARSA*基因.
- 发现了三条与CUD严重程度相关的MA和EA中的三条重要途径.
- 在不同种群中发现重叠的途径 (arylsulfatase激活,heparan硫酸盐降解,p38-gamma/delta信号传递),以及独特的途径 (MA中的整合蛋白β-1,MA/EA中的自身免疫).
结论:
- 在EA,AI和MA种群中,不同的遗传途径有助于CUD严重程度.
- 罕见的功能变异在不同群体的CUD遗传性中发挥着重要作用.
- 存在共同的遗传因素,这强调了在CUD遗传研究中包括多样化的种群的重要性.
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