A comprehensive analysis of NDST3 for schizophrenia and bipolar disorder in Han Chinese.
A comprehensive analysis of NDST3 for schizophrenia and bipolar disorder in Han Chinese.
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汉族精神分裂症和双相情感障碍NDST3综合分析
DOI：
10.1038/tp.2015.199
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发表时间：
2016-01-05
影响因子：
6.8
通讯作者：
Fang Y
中科院分区：
文献类型：
--
作者：
Zhang C;Lu W;Wang Z;Ni J;Zhang J;Tang W;Fang Y
一个新的精神分裂症和双相情感障碍(BD)易感基因座(Rs11098403)在最近的大规模全基因组关联研究中被发现存在于德系犹太人中。Rs11098403位于N-脱乙酰基酶/N-磺基转移酶(肝素氨基葡萄糖基)3(NDST3)编码基因附近。这项研究的目的是在汉族人群中复制这一结果，然后潜在地扩展这些发现。我们进行了两个阶段的研究，以调查NDST3与中国汉族人精神分裂症和BD风险的关系。第一阶段为上海地区632例精神分裂症患者、654例BD患者和684例健康对照。第二阶段为杭州地区522例精神分裂症患者和547例正常人。然后，我们在现有文献的基础上进行了元分析。在阶段1，单核苷酸多态rs11098403与精神分裂症显著相关(校正P=0.005)。精神分裂症患者rs11098403G等位基因频率显著低于对照组(OR=0.68，95%可信区间：0.55−0.84，校正后P=0.002)。BD组和对照组的个体SNP标记基因分型和等位基因分布无显著差异。在第2阶段，rs11098403与精神分裂症的关联被证实(P=0.001，P=0.0003)。合并了1861例精神分裂症患者和2081例对照组的资料后，我们观察到rs11098403G等位基因与精神分裂症有显著关联(Z=5.56，P&t；0.001)，OR=0.70(95%CI：0.61−0.79)。然后，我们进行了表达数量性状基因座分析，以探讨rs11098403对脑内NDST3表达的功能影响。我们观察到rs11098403与Ndst3在海马区的表达显著相关(P=0.027)，尽管在多次测试校正后这种相关性不存在。我们的发现为rs11098403可能改变中国汉族人精神分裂症的遗传风险提供了初步证据。有必要进行进一步的研究，以确定调控中国汉族人大脑NDST3表达的确切机制。这些结果将有助于解释精神分裂症的病理生理机制。
A novel susceptibility locus (rs11098403) for schizophrenia and bipolar disorder (BD) was identified in an Ashkenazi Jewish population by a recent large-scale genome-wide association study. The rs11098403 is located in the vicinity of the gene encoding N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 3,(NDST3). This study aimed to replicate the results in a Han Chinese population and then potentially extend these findings. We performed a two-stage study to investigate the association of NDST3 with the schizophrenia and BD risk in the Han Chinese. In stage 1, a total of 632 patients with schizophrenia, 654 patients with BD and 684 healthy controls were recruited from the Shanghai region. In stage 2, 522 schizophrenia patients and 547 normal subjects were enrolled from the Hangzhou region. Then, we conducted a meta-analysis based on the present literature. In stage 1, the single nucleotide polymorphism (SNP) rs11098403 showed a significant association with schizophrenia (corrected P= 0.005). The frequency of the rs11098403 G allele was significantly lower among schizophrenia patients than among the controls (odds ratio (OR)= 0.68, 95% confidence interval (CI): 0.55− 0.84, corrected P= 0.002). No significant difference was observed in individual SNP marker genotypes or allele distributions between the BD and control groups. In stage 2, the association of rs11098403 with schizophrenia could be validated (genotypic P= 0.001 and allelic P= 0.0003). After pooling all data from 1861 patients with schizophrenia and 2081 controls, we observed a significant association of the rs11098403 G allele with schizophrenia (Z= 5.56, P< 0.001), with an OR= 0.70 (95% CI: 0.61− 0.79). Then, we performed an expression quantitative trait loci analysis to investigate the functional effect of rs11098403 on NDST3 expression in the brain. We observed a significant association of rs11098403 with NDST3 expression in the hippocampus (P= 0.027), although the significance did not survive after multiple testing correction. Our findings provided preliminary evidence that rs11098403 might modify the genetic risk of schizophrenia in the Han Chinese. Further investigations are warranted to identify the precise mechanism regulating brain NDST3 expression in the Han Chinese. These results would help to explain the pathophysiological mechanism of schizophrenia.
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影响因子：
44.1
作者：
Shi, YY;He, L
通讯作者：
He, L
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作者：
Stefansson, H;Sarginson, J;St Clair, D
通讯作者：
St Clair, D
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