CACNA1C变种与神经精神疾病的类关联
Zuxing Wang1,2, Xiandong Lin3, Xinqun Luo4
1Shanghai Mental Health Center, Shanghai Jiao Tong University School of medicine, Shanghai 200030, China.
Schizophrenia bulletin
|June 12, 2023
概括
CACNA1C的遗传变异与多种神经精神疾病有关,特别是精神分裂症和双相情感障碍. 这些发现表明,CACNA1C在这些疾病的共同遗传风险和大脑结构中起作用.
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
- 大脑成像遗传学
背景情况:
- 神经精神疾病表现出高遗传性与共享的遗传因素.
- 通过全基因组关联研究,CACNA1C基因中的单核酸多态 (SNP) 已与各种神经精神疾病有关.
研究的目的:
- 调查13种神经精神疾病中CACNA1C基因内的与疾病相关的SNP重叠情况.
- 为了检查死后脑样本中的CACNA1CmRNA表达.
- 评估共享风险等位基因与大脑结构指标的关联.
主要方法:
- 在CACNA1C.中对来自37个群体的70,711名受试者进行疾病相关SNP的元分析.
- 在五个死后大脑队列中对CACNA1CmRNA的差异基因表达分析.
- 风险等位基因与总内体积 (ICV),灰质体积 (GMV),皮质表面积 (SA) 和皮质厚度 (TH) 的关联测试.
主要成果:
- 18个CACNA1CSNP显示了与多种疾病的标称关联;五个SNP在精神分裂症,双相情感障碍和酒精使用障碍的错误发现率纠正中幸存下来.
- 在精神分裂症,双相情感障碍和帕金森病患者的大脑中,CACNA1C mRNA的表达差异化.
- 分享风险等位基因与大脑结构变异 (ICV,GMV,SA,TH) 有显著的关联.
结论:
- CACNA1C变异与多种精神疾病有关,精神分裂症和双相情感障碍最为严重.
- CACNA1C可能会导致这些疾病背后的共同遗传风险和病理生理学.
- 这些发现整合了遗传关联,基因表达和大脑结构,以阐明CACNA1C在神经精神疾病中的作用.
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