Association of MSI2 Gene Polymorphism with Age-at-Onset of Schizophrenia in a Chinese Population.
Association of MSI2 Gene Polymorphism with Age-at-Onset of Schizophrenia in a Chinese Population.
复制标题
MSI2 基因多态性与中国人群精神分裂症发病年龄的关联。
DOI：
10.1007/s12264-017-0176-4
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发表时间：
2017
影响因子：
5.6
通讯作者：
Zhang Dai
中科院分区：
文献类型：
--
作者：
Luan Zhi-Lin;Cui Xiao-Hui;Xu Hu;Lu He-Yuan;Li Yu-Yuan;Lu Tian-Lan;Zhang Dai
精神分裂症是精神病学家和心理健康照顾者面临的最复杂和最具挑战性的精神障碍之一。这对患者来说是一个沉重的负担，通常发生在成年期间。精神分裂症的发病高峰期在18-25岁，导致生产力丧失，给亲属带来相当大的负担，并造成高昂的医疗和社会成本。在全球普通人群中，精神分裂症的生命风险约为1%[1]。精神分裂症有很强的遗传成分，遗传流行病学研究一直表明这一点[2]。尽管遗传风险很高，但单靠基因影响并不能完全决定精神分裂症的病因。据估计，精神分裂症的遗传率在66%到85%之间，为环境因素的贡献留下了空间。精神分裂症的遗传模式表明，精神分裂症是一种非孟德尔式的传播方式，使简单的主基因依赖成为可能。相反，多基因模型似乎提供了更好的解释[3]。人类MSI2基因是武藏基因家族的成员，该基因编码一组进化保守的神经RNA结合蛋白。MSI2受发育调节，主要在神经干细胞中表达，在胚胎神经发育过程中对细胞命运的决定很重要[4]。人类MSI2基因位于染色体17q上，这是精神分裂症的潜在易感区域[5]。我们先前在中国汉族人中进行的全基因组关联研究显示MSI2与精神分裂症之间存在中度关联[6]。进一步的重复和联合关联研究显示，三个MSI2标签SNPs(rs9892791、rs11657292和rs1822381)与精神分裂症易感性显著相关[7]。发病年龄被认为是精神分裂症病因学最有价值的线索之一。几项全基因组连锁研究证实了精神分裂症发病年龄的遗传因素[8]。Cardno等人进行的全基因组连锁研究。在染色体17q(D17S787)[9]上有一个最高的LOD评分，接近MSI2基因区。在此，我们旨在研究三个MSI2标签SNPs与中国汉族精神分裂症患者的发病年龄之间的潜在关联。612例精神分裂症患者来自北京大学精神卫生研究所，北京，中国。所有患者都是由至少两名有经验的精神病学家根据《精神疾病诊断和统计手册》第四版(DSM-IV)标准进行诊断的。没有一人出现严重的医疗并发症。在参与之前，患者或他们的监护人在确保他们
Schizophrenia is one of the most complicated and challenging mental disorders psychiatrists and mental health caregivers confront. It is a heavy burden for the patients and usually occurs during adulthood. With a peak age-atonset of 18–25 years, schizophrenia results in the loss of productivity, poses a considerable burden on the relatives, and causes high medical and social costs. In the general population worldwide, the life risk for schizophrenia is about 1%[1]. Schizophrenia has a strong genetic component, which has been consistently indicated by genetic epidemiological studies [2]. In spite of high genetic risk, genetic influence alone does not fully determine the etiology of schizophrenia. It has been estimated that the heritability of schizophrenia ranges from 66% to 85%, leaving space for the contribution of environmental factors.The inheritance pattern of schizophrenia suggests a non-Mendelian mode of transmission and makes simple major gene dependency impossible. Instead, a polygenic model seems to provide a better explanation [3]. The human MSI2 gene is a member of the Musashi gene family which encodes an evolutionarily conserved group of neural RNA-binding proteins. MSI2 is developmentally regulated, predominantly expressed in neural stem cells, and important for cell fate determination during embryonic neurodevelopment [4]. The human MSI2 gene is located on chromosome 17q, a potential susceptibility region for schizophrenia [5]. Our previous genome-wide association study (GWAS) in a Han Chinese population revealed a moderate association of MSI2 and schizophrenia [6]. A further replication and combined association study showed significant association of three MSI2 tag SNPs (rs9892791, rs11657292, and rs1822381) with schizophrenia susceptibility [7]. Age-at-onset is considered as one of the most valuable clues to the etiology of schizophrenia. A genetic contribution to the age-at-onset of schizophrenia was confirmed by several genome-wide linkage studies [8]. A genome-wide linkage study conducted by Cardno et al. indicated a peak LOD score on chromosome 17q (D17S787)[9], close to the MSI2 gene region. Here, we aimed to investigate the potential association between three MSI2 tag SNPs and age-at-onset of schizophrenia in a Han Chinese sample of schizophrenia patients. Six hundred and twelve schizophrenia patients were recruited from the Institute of Mental Health, Peking University, Beijing, China. All the patients were diagnosed in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria by at least two experienced psychiatrists. None had severe medical complications. Prior to participation, the patients or their guardians gave written consent after ensuring they