Linkage and association of schizophrenia with genetic variations in the locus of neuregulin 1 in Korean population
Linkage and association of schizophrenia with genetic variations in the locus of neuregulin 1 in Korean population
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DOI：
10.1002/ajmg.b.30209
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发表时间：
2006-04-05
影响因子：
2.8
通讯作者：
Hong, KS
中科院分区：
文献类型：
--
作者：
Kim, JW;Lee, YS;Hong, KS
据报道，基于全基因组连锁扫描，染色体8p21-12是精神分裂症的易感性位点。神经调节蛋白1 （NRG1）在这一位点被确定为精神分裂症的位置候选基因后，一些独立的关联研究报告了有争议的结果。为了确定该位点的遗传变异是否与韩国人群的精神分裂症有关，我们使用连锁和关联分析调查了多个家族和不相关的患者。对40个精神分裂症家庭的8p21-12微卫星标记进行基因分型，并应用非参数连锁分析。对242例无血缘关系的精神分裂症患者和相同数量的正常对照进行了3个单核苷酸多态性（snp）、2个微卫星标记及其单倍型的关联研究。D8S1769位于NRG1第一个外显子5′端上游352 kb处，在三种被采用的表型类别中，有两种（“狭窄”和“狭窄伴有幻听（AH）”）存在显著的连锁信号。在关联研究中，SNP8NRG241930的G等位基因在AHs患者亚组中显著过量。我们还发现与精神分裂症相关的单倍型具有保护作用。这项研究为nrg1位点8p12的遗传变异与精神分裂症的联系和关联提供了额外的证据。NRG1可能在精神分裂症易感性中发挥作用，也可能与这种疾病的因果位点存在连锁不平衡（LD）。(c) 2006 Wiley-Liss, Inc。
Chromosome 8p21-12 has been reported to be a susceptibility locus for schizophrenia based on genome-wide linkage scans. After neuregulin 1 (NRG1) was identified as a positional candidate gene for schizophrenia in this locus, several independent association studies have reported controversial results. To determine whether genetic variations in this locus are associated with schizophrenia in the Korean population, we investigated multiplex families and unrelated patients using linkage and association analyses. Seven microsatellite markers in 8p21-12 were genotyped for 40 families with schizophrenia, and a non-parametric linkage analysis was applied. The association study was performed with 242 unrelated schizophrenia patients and the same number of normal controls for three single nucleotide polymorphisms (SNPs), two microsatellite markers and their haplotypes. A significant linkage signal was observed on D8S1769, which is located 352 kb upstream of the 5' end of the first exon of NRG1 for two ("narrow," and "narrow with auditory hallucination (AH)") of the three adopted phenotype classes. In the association study, the G allele of SNP8NRG241930 was significantly in excess in the subgroup of patients with AHs. We also found haplotypes which were associated with schizophrenia with a protective effect. This study provides additional suggestive evidence for both the linkage and association of genetic variations on 8p12, a locus of NRG 1, with schizophrenia. NRG1 might either play a role in the predisposition to schizophrenia or be in linkage disequilibrium (LD) with a causal locus of this illness. (c) 2006 Wiley-Liss, Inc.