基于区域的功能注释分析确定了与印度南亚人认知功能相关的基因
Hasan Abu-Amara1, Wei Zhao1, Zheng Li1
1University of Michigan.
Research square
|August 16, 2024
概括
南亚人痴呆的遗传风险因素尚未得到充分研究. 这项研究发现,欧洲祖先群体中的一些阿尔茨海默病 (AD) 风险基因也与印度南亚人的认知功能有关.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 人口健康 人口健康
背景情况:
- 南亚人中痴呆的发病率很高 (在60岁以上的人群中为7.4%),但遗传风险因素在很大程度上仍未知.
- 大多数已识别的阿尔茨海默病 (AD) 风险位源自欧洲祖先 (EA) 研究,限制了对不同人群的适用性.
研究的目的:
- 通过使用全基因组序列数据,研究南亚人认知功能遗传风险因素.
- 识别基因的关联与认知措施,包括印度语精神状态检查 (HMSE) 和一般认知功能.
主要方法:
- 分析了印度长度衰老研究 (LASI-DAD) 的2680名参与者的全基因组序列数据.
- 在EA种群中对84个与AD相关的基因进行了基因关联测试,检查了误解/功能丧失 (LoF) 和促进剂/增强剂变异.
- 使用注释权重和没有注释权重的使用注释信息Rmation (STAAR) 的变异组关联测试.
主要成果:
- 在误解/LoF分析中,三个基因与认知功能指标 (FDR q<0.1) 有显著的关联: *APOE* (4个指标), *PICALM* (HMSE得分) 和 *TSPOAP1* (执行功能).
- 确定了特定的变异,包括PICALM*中罕见的误解突变rs779406084,该突变在南亚队列中比在EA中更为普遍.
- 对于特定于大脑的促进剂/增强剂变体,没有发现显著的关联.
结论:
- 在EA群体中先前与AD相关的基因中的Missense/LoF变异与印度南亚人的认知功能有关.
- 全基因组测序有助于发现潜在的新型因果变异,这些变异可能在南亚人群中得到丰富.
- 研究结果强调了研究多样化的群体的重要性,以了解痴呆症和认知衰退的遗传结构.
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