| 1 | Nat. Genet. 2011 Dec 43: 1228-31 |
|---|---|
| PMID | 22037552 |
| 标题 | Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. |
| Abstract | To identify susceptibility loci forschizophrenia，我们进行了两阶段全基因组关联研究（GWAS）schizophrenia在汉族人口中（GWAS：746个人schizophrenia和1,599个健康对照；验证：4,027个人schizophreniaand 5,603 healthy controls). We identified two susceptibility loci forschizophreniaat 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 � 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon ofNKAPL, P(combined) = 6.91 � 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 � 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 � 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 � 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 � 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci forschizophrenia汉族人口为6p21-p22.1。我们发现NKAPLand ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis ofschizophrenia。 |
| SCZ关键字 | schizophrenia |
| 2 | PLOS ONE 2013 -1 8：E56732 |
| PMID | 23437227 |
| 标题 | Replication of association between schizophrenia and chromosome 6p21-6p22.1 polymorphisms in Chinese Han population. |
| Abstract | 跨越扩展的主要组织相容性复合物（MHC）区域的6P21-P22.1染色体是一个高度多态的基因致密区域。它已被确定为schizophrenia在欧洲人，日本和中文。在我们以前的两阶段全基因组关联研究（GWAS）中，锌指的多态性与KRAB和扫描结构域4（ZKSCAN4），核因子 - b-激活蛋白样（NKAPL）和PiggyBac转座元件得出的1（PGBD1），定位于6p21-P22.1染色体，与schizophrenia。进一步研究协会tween polymorphisms at this locus andschizophreniain the Chinese Han population, we selected eight other single-nucleotide polymorphisms (SNPs) distributed in or near these genes for a case-control association study in an independent sample of 902 cases and 1,091 healthy controls in an attempt to replicate the GWAS results. Four of these eight SNPs (rs12214383, rs1150724, rs3800324, and rs1997660) displayed a nominal difference in allele frequencies between the case and control groups. The association between two of these SNPs andschizophrenia即使在Bonferroni校正后也很明显（RS12000：等位基因A> G，P = 2.50E-04，优势比[OR] = 1.27，95％置信区间[CI] = 1.12-1.45; RS1150722：RS1150722：ALLELE C> T，P = =4.28e-05，OR = 0.55，95％CI = 0.41-0.73）。单倍型AttGACGC，包括这八个SNP（RS2235359，RS2185955，RS12214383，RS12000，RS1150724，RS1150724，RS1150722，RS1150722，RS3800324和RS3800324和RS1997660），RS1150722显着相关。schizophrenia(P = 6.60E-05). We also performed a combined study of this replication sample and the first-stage GWAS sample. The combined study revealed that rs12000 and rs1150722 were still strongly associated withschizophrenia(rs12000: allele G>A, P(combined) = 0.0019, OR = 0.81; rs1150722: allele G>A, P(combined) = 3.00E-04, OR = 0.61). These results support our findings that locus 6p21-p22.1 is significantly associated withschizophreniain the Chinese Han population and encourage further studies of the functions of these genetic factors. |
| SCZ关键字 | schizophrenia |
| 3 | Schizophr. Res. 2014 Aug 157: 169-74 |
| PMID | 24972756 |
| 标题 | Resequencing and association study of the NFKB activating protein-like gene (NKAPL) in schizophrenia. |
| Abstract | schizophreniais a highly inheritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Recently, in the Han Chinese population, a SNP rs1635 located within the exon of theNKAPLgene (encoding NFKB activating protein-like) achieved genome-wide significance inschizophrenia。 In order to find the causal variants of theNKAPLgene inschizophrenia，我们在启动子区域中搜索了遗传变异，外显子（包括两个UTR末端）使用直接测序schizophrenia(n=515) and non-psychotic controls (n=456), all Han Chinese from Taiwan, and conducted an association and rudimentary functional study. We identified 5 common SNPs (defined as minor allele frequency (MAF)>0.01) in theNKAPLgene. In a case-control association analysis, the minor allele (A) of rs1635 was significantly more common among patients than controls (P=0.0003, OR=1.41, 95% CI=1.17-1.71). A haplotype analysis of the 5 common SNPs indicated a risk haplotype (rs12000C-rs1635A-rs9461446C-rs3734564G-rs1679709G) associated withschizophrenia（p = 2.77E-005，OR = 1.53，95％CI = 1.25-1.87）。此外，我们确定了4个患者特定的稀有SNP（MAF <0.01）（C.137G> A，C.213G> A，C.752C> T（RS370337122）和C.844G> a（RS147161729））NKAPLgene. In silico analysis demonstrated their functional impact on the protein; however, there was also 1 control-specific rare SNP (c.119G>A) detected within theNKAPL基因，表明这些推定病理稀有SNP的临床相关性并不直接。 This study suggested that rs1635 in theNKAPLgene appeared to play a role in conferring susceptibility toschizophrenia。In addition, some rare SNPs in theNKAPLgene with possibly damaging effects may be important in our patients. Our study provides genetic clues to indicate the involvement ofNKAPLinschizophrenia。 |
| SCZ关键字 | schizophrenia |
| 4 | Neurosci. Lett. 2015 Sep 605: 49-52 |
| PMID | 26297123 |
| 标题 | 支持NKAPL与精神分裂症的关联的进一步证据。 |
| Abstract | schizophrenia(SZ) is a severe chronic mental disorder with complex genetic mechanisms. Increasing evidence implicate immune system dysfunction in the pathogenesis of SZ. The non-synonymous single nucleotide polymorphism (SNP) rs1635 inNKAPL, was identified by a genome-wide association study (GWAS) for SZ in Han Chinese from north China. A replication study failed to detect the association of rs1635 with SZ in Han Chinese from central south of China, while another one confirmed the positive association in Han Chinese from Taiwan. To further clarify these findings, we conducted a case-control association study of rs1635 in a cohort of Han Chinese from east China, including 1406 SZ cases and 1136 healthy controls. We detected a positive association of rs1635 with SZ, with the major allele (G) of rs1635 conferring a risk for SZ (P=0.033, OR=1.14). Our findings add further evidence for the involvement ofNKAPLpolymorphisms in the development of SZ. |
| SCZ关键字 | schizophrenia |