Kim Jong Won, Lee Yu-Sang, Cho Eun-Young, Jang Yong Lee, Park Dong Yeon, Choi Kyeong-Sook, Jeun Hyun Ok, Cho Seung-Hee, Jang Sue-Yon, Hong Kyung Sue
Department of Laboratory Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
Am J Med Genet B Neuropsychiatr Genet. 2006 Apr 5;141B(3):281-6. doi: 10.1002/ajmg.b.30209.
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 NRG1, 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.
基于全基因组连锁扫描，8号染色体p21 - 12区域已被报道为精神分裂症的一个易感基因座。在神经调节蛋白1（NRG1）被确定为该基因座中精神分裂症的一个定位候选基因后，多项独立的关联研究报告了相互矛盾的结果。为了确定该基因座的基因变异是否与韩国人群的精神分裂症相关，我们使用连锁和关联分析对多个核心家系及散发病例进行了研究。对40个精神分裂症家系的8号染色体p21 - 12区域的7个微卫星标记进行基因分型，并应用非参数连锁分析。关联研究在242例散发性精神分裂症患者和相同数量的正常对照中进行，检测了3个单核苷酸多态性（SNP）、2个微卫星标记及其单倍型。在D8S1769上观察到显著的连锁信号，该标记位于NRG1第一个外显子5'端上游352 kb处，在所采用的三种表型分类中的两种（“狭义”和“伴有幻听（AH）的狭义”）中出现。在关联研究中，SNP8NRG241930的G等位基因在伴有幻听的患者亚组中显著过量。我们还发现了与精神分裂症相关且具有保护作用的单倍型。本研究为8p12区域（NRG1的一个基因座）的基因变异与精神分裂症的连锁和关联提供了更多的提示性证据。NRG1可能在精神分裂症的易感性中起作用，或者与该疾病的致病基因座处于连锁不平衡（LD）状态。
