遗传相关性分析确定TMEM106B,ACE和ERC2是阿尔茨海默氏症和初级精神疾病之间共享的遗传位置
Ajneesh Kumar1,2, Nicholas R Ray1,2, Jiji T Kurup1,2
1Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.
概括
遗传分析揭示了阿尔茨海默病 (AD) 与抑郁症和焦虑症等精神疾病之间的共同变异. 这一发现为AD神经精神病症状的常见原因和潜在的新疗法提供了洞察力.
科学领域:
- 神经遗传学 神经遗传学
- 精神病学遗传学 精神病学遗传学
- 计算生物学 计算生物学
背景情况:
- 神经精神症状 (NPS) 在阿尔茨海默病 (AD) 中很普遍,影响高达85%的患者.
- 目前对阿尔茨海默氏症的NPS治疗方法通常是无效的,原因是对潜在原因的理解有限,以及与精神疾病的潜在遗传重叠.
研究的目的:
- 研究阿尔茨海默病与主要精神疾病之间共同病因的遗传基础.
- 确定特定的分子途径和遗传变异,有助于AD和精神疾病的同时发生.
主要方法:
- 来自大型队伍的全基因组关联研究 (GWAS) 总结统计数据用于阿尔茨海默病,抑郁症,精神分裂症,双相情感障碍和焦虑症.
- 使用MiXeR和局部[co]变量注释分析 (LAVAN) 进行了遗传相关性分析,以评估共享的遗传影响.
主要成果:
- 在TMEM106B (rs3173615) 中的一个误解变体被确定为AD,抑郁和焦虑之间的共享.
- 在ACE (rs4292) 中的一个调节变体显示了AD和精神分裂症之间的共同遗传影响.
- 发现ERC2中的两个变体 (rs17288728; rs815460) 与无意义介导的mRNA衰变相关,在AD和焦虑之间是共享的.
结论:
- 鉴定的遗传变异和相关的分子途径突出显示了AD和精神疾病之间的共同病因组件.
- 这些发现为开发更有针对性,更有效的治疗策略为AD神经精神病症状提供了基础.
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