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 Zhao1,2, Zheng Li3
1Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
medRxiv : the preprint server for health sciences
|January 31, 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 遗传学 是一个
- 神经科学是一个神经科学.
- 人口健康 人口健康
背景情况:
- 在南亚人中痴呆的患病率很高 (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然未知.
- 大多数已知的阿尔茨海默病 (AD) 风险位在欧洲祖先 (EA) 种群中被确定,这限制了对南亚人的适用性.
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的遗传风险因素.
- 识别基因相关联与认知指标,包括印度语精神状态考试 (HMSE) 评分和一般认知功能.
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分析,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 (APOE,PICALM,TSPOAP1) 与认知功能指标有显著的关联 (FDR q<0.1).
- APOE与四个认知指标相关,PICALM与HMSE得分相关,TSPOAP1与执行功能相关.
- 与EA相比,在南亚人群中发现了PICALM (rs779406084) 丰富的罕见误解变异.
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.
- 整个基因组测序可以识别潜在的新型因果变异认知衰退,这些变异在像南亚人这样的特定人群中是丰富的.
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