Department of Forensic Psychiatry, School of Medicine & Forensics, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, China; Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine & Forensics, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, China.
Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, China.
Schizophr Res. 2019 Apr;206:407-412. doi: 10.1016/j.schres.2018.10.011. Epub 2018 Oct 23.
Altered cholinergic neural transmission is hypothesized to increase susceptibility to cognitive deficits in psychotic disorders such as schizophrenia (SCZ). The nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) is reported to be associated with cognitive function in nicotine-dependent populations and SCZ in non-smoking SCZ patients. Nevertheless, it is still not clear whether the CHRNA5 gene contributes to susceptibility to the cognitive deficits of SCZ without smoking. To further clarify the role of CHRNA5, we designed a two-stage, case-control study to examine the association between CHRNA5 and SCZ and its clinical features adjusted for smoking status in early-onset SCZ patients. A total of 15 tag single nucleotide polymorphisms (SNPs) on CHRNA5 were genotyped in the discovery stage, which included 485 early-onset SCZ patients and 1018 controls, and then, we replicated this association in a confirmatory population of 674 patients and 1886 controls. The rs16969968 SNP was identified as significantly associated with SCZ in both datasets. In addition, the severity of psychotic symptoms and cognitive deficits was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Wisconsin Card Sorting Test (WCST). The rs16969968 SNP was associated with psychotic symptoms in patients and with cognitive function in patients and controls. Our results show that rs16969968 on CHRNA5 is tightly linked to genetic susceptibility, psychotic symptoms and cognitive deficits in SCZ in an early-onset Chinese population, suggesting that CHRNA5 may play an important role in the etiology of SCZ.
胆碱能神经传递的改变被假设会增加精神分裂症（SCZ）等精神障碍患者认知缺陷的易感性。据报道，烟碱型乙酰胆碱受体α5 亚基基因（CHRNA5）与尼古丁依赖人群的认知功能和非吸烟 SCZ 患者的 SCZ 有关。然而，CHRNA5 基因是否会导致非吸烟 SCZ 患者的认知缺陷易感性，目前仍不清楚。为了进一步阐明 CHRNA5 的作用，我们设计了一个两阶段的病例对照研究，以检查 CHRNA5 与 SCZ 及其在早期发病的 SCZ 患者中调整吸烟状况后的临床特征之间的关联。在发现阶段，共对 CHRNA5 上的 15 个标签单核苷酸多态性（SNP）进行了基因分型，包括 485 例早期发病的 SCZ 患者和 1018 例对照者，然后在一个包含 674 例患者和 1886 例对照者的确认人群中对这种关联进行了复制。rs16969968 单核苷酸多态性在两个数据集都被确定与 SCZ 显著相关。此外，使用阳性和阴性症状量表（PANSS）和威斯康星卡片分类测验（WCST）评估精神症状和认知缺陷的严重程度。rs16969968 单核苷酸多态性与患者的精神症状以及患者和对照者的认知功能有关。我们的结果表明，CHRNA5 上的 rs16969968 与中国早期发病人群中 SCZ 的遗传易感性、精神症状和认知缺陷密切相关，提示 CHRNA5 可能在 SCZ 的发病机制中发挥重要作用。
