Association of ARHGAP18 polymorphisms with schizophrenia in the Chinese-Han population.
Association of ARHGAP18 polymorphisms with schizophrenia in the Chinese-Han population.
复制标题
ARHGAP18 多态性与中国汉族人群精神分裂症的关联。
DOI：
10.1371/journal.pone.0175209
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Lv L
中科院分区：
文献类型：
--
作者：
Guo W;Cai Y;Zhang H;Yang Y;Yang G;Wang X;Zhao J;Lin J;Zhu J;Li W;Lv L
通过病例对照和全基因组关联研究发现，许多发育基因与精神分裂症（SZ）相关，提示神经发育障碍是SZ的主要致病机制。然而，没有神经发育缺陷与SZ发生明确相关，可能是由于疾病异质性和不同种族间各种基因变异的差异效应。因此，关键是要研究特定民族人口，如汉族人的联系。新发现的RhoGAP ARHGAP 18可能通过调节RhoA/C参与神经发育。在此，我们描述了在汉族人群中与SZ相关的ARHGAP 18的四个单核苷酸多态性（SNPs），该队列包括2000例以上的病例和对照。两个SNPs rs7758025和rs 9483050在病例组和对照组之间的基因型（P = 0.0002和P = 7.54×10−6）和等位基因频率（P = 4.36×10−5和P = 5.98×10−7）均显示出显著差异。rs7758025-rs 9385502中的AG单倍型与SZ的发生密切相关（P = 0.0012，OR = 0.67，95%CI = 0.48-0.93），这种关联在1000次随机排列检验后仍然存在（P = 0.022）。在独立收集的验证队列中，rs 9483050是与SZ最强相关的SNP。此外，rs 12197901的等位基因频率在合并队列中仍然与SZ相关（P = 0.021），尽管在单独的验证队列中不相关（P = 0.251）。总的来说，我们的数据表明，ARHGAP 18可能赋予SZ在中国汉族人群中的脆弱性，提供了额外的证据参与精神分裂症的发病机制中的神经发育功能障碍。
Numerous developmental genes have been linked to schizophrenia (SZ) by case-control and genome-wide association studies, suggesting that neurodevelopmental disturbances are major pathogenic mechanisms. However, no neurodevelopmental deficit has been definitively linked to SZ occurrence, likely due to disease heterogeneity and the differential effects of various gene variants across ethnicities. Hence, it is critical to examine linkages in specific ethnic populations, such as Han Chinese. The newly identified RhoGAP ARHGAP18 is likely involved in neurodevelopment through regulation of RhoA/C. Here we describe four single nucleotide polymorphisms (SNPs) in ARHGAP18 associated with SZ across a cohort of >2000 cases and controls from the Han population. Two SNPs, rs7758025 and rs9483050, displayed significant differences between case and control groups both in genotype (P = 0.0002 and P = 7.54×10−6) and allelic frequencies (P = 4.36×10−5 and P = 5.98×10−7), respectively. The AG haplotype in rs7758025−rs9385502 was strongly associated with the occurrence of SZ (P = 0.0012, OR = 0.67, 95% CI = 0.48–0.93), an association that still held following a 1000-times random permutation test (P = 0.022). In an independently collected validation cohort, rs9483050 was the SNP most strongly associated with SZ. In addition, the allelic frequencies of rs12197901 remained associated with SZ in the combined cohort (P = 0.021), although not in the validation cohort alone (P = 0.251). Collectively, our data suggest the ARHGAP18 may confer vulnerability to SZ in the Chinese Han population, providing additional evidence for the involvement of neurodevelopmental dysfunction in the pathogenesis of schizophrenia.