| 1 | Nat Commun 2013 -1 4：2739 |
|---|---|
| PMID | 24253340 |
| 标题 | Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder. |
| 抽象的 | schizophrenia躁郁症和双相情感障碍是具有较高遗传力和重叠遗传方差的主要精神疾病。在这里，我们在904的种族均质队列中进行全基因组的关联研究schizophreniacases and 1,640 controls drawn from the Ashkenazi Jewish population. We identify a novel genome-wide significant risk locus at chromosome 4q26, demonstrating the potential advantages of this founder population for gene discovery. The top single-nucleotide polymorphism (SNP; rs11098403) demonstrates consistent effects across 11 replication and extension cohorts, totalling 23, 191 samples across multiple ethnicities, regardless of diagnosis (schizophrenia或双相情感障碍），导致pMETA = 9.49�10（-12）（优势比（OR）= 1.13，95％置信区间（CI）：1.08-1.17），pMETA = 2.67 = 2.67 - 10（-8）（OR = 1.15，95％CI：1.08-1.21）schizophrenia独自的。此外，该基因间SNP显着预测了尸体后小脑基因的表达NDST3，它编码对硫酸乙酰肝素代谢至关重要的酶。硫酸乙酰肝素结合对于神经突生长，轴突形成和突触过程至关重要。 |
| SCZ关键字 | schizophrenia |
| 2 | Neurosci. Lett. 2014 Oct 581: 42-5 |
| PMID | 25139529 |
| 标题 | rs11098403 polymorphism near NDST3 is associated with a reduced risk of schizophrenia in a Han Chinese population. |
| 抽象的 | A recent genome-wide association study indicated that rs11098403, a single nucleotide polymorphism in the vicinity ofNDST3，与schizophrenia在高加索人。但是，这种关系尚未在其他人群或族裔群体中得到验证。本文中，我们进行了一项病例对照研究，以研究RS11098403多态性的关联schizophreniarisk in a Han Chinese population comprising 440schizophreniapatients and 450 control subjects. For the first time, we showed that the minor allele (G) of rs11098403 is closely associated with a reduced risk ofschizophrenia(OR=0.614; 95% CI: 0.453-0.833; P=0.002; Power=0.832). Meanwhile, the G allele of rs11098403 seemed to reduce theschizophrenia通过主导方式（GG+Ag vs. AA，OR = 0.526; 95％CI：0.374-0.74; P <0.001）的风险。此外，使用包含267的独立复制样本进一步证实了这种关联schizophreniapatients and 400 control subjects with a Han Chinese descent (OR=0.652; 95% CI: 0.469-0.907; P=0.011; Power=0.772). Taken together, these findings demonstrate a significant association between rs11098403 andschizophrenia汉族中国人的风险，确认先前从白种人获得的数据。 |
| SCZ关键字 | schizophrenia |
| 3 | Mol Cytogenet 2015 -1 8: 46 |
| PMID | 26136833 |
| 标题 | 评估精神分裂症患者脑基因组中拷贝数变化。 |
| 抽象的 | Cytogenomic mutations and chromosomal abnormality are implicated in the neuropathology of several brain diseases. Cell ?heterogeneity of brain tissues makes their detection and validation difficult, however. In the present study, we analyzed gene dosage alterations in brain DNA ofschizophrenia并比较那些鉴定出拷贝数变化（CNV）的患者schizophrenia患者以及亚洲淋巴细胞DNA中的患者，并试图获得有关细胞基因组不稳定性的病理贡献的暗示schizophrenia. Brain DNA was extracted from postmortem striatum ofschizophreniapatients and control subjects (n?=?48 each) and subjected to the direct two color microarray analysis that limits technical data variations. Disease-associated biases of relative DNA doses were statistically analyzed with Bonferroni's compensation on the premise of brain cell mosaicism. We found that the relative gene dosage of 85 regions significantly varied among a million of probe sites. In the candidate CNV regions, 26 regions had no overlaps with the common CNVs found in Asian populations and included the genes (i.e., ANTXRL, CHST9, DNM3,NDST3, SDK1, STRC, SKY) that are associated withschizophreniaand/or other psychiatric diseases. The majority of these candidate CNVs exhibited high statistical probabilities but their signal differences in gene dosage were less than 1.5-fold. For test evaluation, we rather selected the 10 candidate CNV regions that exhibited higher aberration scores or larger global effects and were thus confirmable by PCR. Quantitative PCR verified the loss of gene dosage at two loci (1p36.21 and 1p13.3) and confirmed the global variation of the copy number distributions at two loci (11p15.4 and 13q21.1), both indicating the utility of the present strategy. These test loci, however, exhibited the same somatic CNV patterns in the other brain region. The present study lists the candidate regions potentially representing cytogenomic CNVs in the brain ofschizophreniapatients, although the significant but modest alterations in their brain genome doses largely remain to be characterized further. |
| SCZ关键字 | schizophrenia |
| 4 | Transl Psychiatry 2016 -1 6: e701 |
| PMID | 26731438 |
| 标题 | A comprehensive analysis of NDST3 for schizophrenia and bipolar disorder in Han Chinese. |
| 抽象的 | A novel susceptibility locus (rs11098403) forschizophreniaand 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)。本研究旨在复制结果s in a Han Chinese population and then potentially extend these findings. We performed a two-stage study to investigate the association ofNDST3with theschizophrenia和汉族中国的BD风险。在第1阶段，共有632例患者schizophrenia，从上海地区招募了654例BD患者和684例健康对照。在第2阶段，522schizophrenia杭州地区招募了患者和547名正常受试者。然后，我们根据目前的文献进行了荟萃分析。在第1阶段，单核苷酸多态性（SNP）RS11098403显示与schizophrenia(corrected P=0.005). The frequency of the rs11098403 G allele was significantly lower amongschizophreniapatients 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 withschizophreniacould be validated (genotypic P=0.001 and allelic P=0.0003). After pooling all data from 1861 patients withschizophrenia和2081个对照，我们观察到RS11098403 g等位基因与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 onNDST3在大脑中的表达。我们观察到RS11098403与NDST3尽管显着性在多次测试校正后没有生存，但海马中的表达（p = 0.027）。我们的发现提供了初步证据，表明RS11098403可能会改变schizophreniain the Han Chinese. Further investigations are warranted to identify the precise mechanism regulating brainNDST3expression in the Han Chinese. These results would help to explain the pathophysiological mechanism ofschizophrenia. |
| SCZ关键字 | schizophrenia |