Department of Psychiatry, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Am J Med Genet B Neuropsychiatr Genet. 2010 Apr 5;153B(3):786-91. doi: 10.1002/ajmg.b.31048.
Chromosome 22q13 region has been implicated in schizophrenia in several linkage studies. Genes within this locus are therefore promising genetic and biologic candidate genes for schizophrenia if they are expressed in the brain or predicted to have some role in brain development. A recent study reported that bromodomain-containing 1 gene (BRD1), located in 22q13, showed an association with schizophrenia in a Scottish population. Except for being a putative regulator of transcription, the precise function of BRD1 is not clear; however, expression analysis of BRD1 mRNA revealed widespread expression in mammalian brains. In our study, we explored the association of BRD1 with schizophrenia in a Japanese population (626 cases and 770 controls). In this association analysis, we first examined 10 directly genotyped single-nucleotide polymorphisms (SNPs) and 20 imputed SNPs. Second, we compared the BRD1 mRNA levels between cases and controls using lymphoblastoid cell lines (LCLs) derived from 29 cases and 30 controls. Although the SNP (rs138880) that previously has been associated with schizophrenia showed the same trend in the Japanese population, no significant association was detected between BRD1 and schizophrenia in our study. Similarly, no significant differences in BRD1 mRNA levels in LCLs were detected. Taken together, we could not strongly show that common SNPs in the BRD1 gene account for a substantial proportion of the genetic risk for schizophrenia in the Japanese population.
22q13 染色体区域在几项连锁研究中与精神分裂症有关。如果该基因座内的基因在大脑中表达或预测在大脑发育中有某种作用,那么它们就是精神分裂症有希望的遗传和生物学候选基因。最近的一项研究报告称,位于 22q13 的溴结构域蛋白 1 基因 (BRD1) 在苏格兰人群中与精神分裂症有关。除了可能是转录的调节因子外,BRD1 的精确功能尚不清楚;然而,BRD1mRNA 的表达分析显示其在哺乳动物大脑中有广泛的表达。在我们的研究中,我们在日本人群(626 例病例和 770 例对照)中探讨了 BRD1 与精神分裂症的关联。在这项关联分析中,我们首先检查了 10 个直接基因分型的单核苷酸多态性 (SNP) 和 20 个推断的 SNP。其次,我们使用源自 29 例病例和 30 例对照的淋巴母细胞系 (LCL) 比较了病例和对照之间的 BRD1mRNA 水平。虽然先前与精神分裂症相关的 SNP(rs138880) 在日本人群中也表现出相同的趋势,但我们的研究未发现 BRD1 与精神分裂症之间存在显著关联。同样,LCL 中 BRD1mRNA 水平也没有检测到显著差异。综上所述,我们不能强烈表明 BRD1 基因中的常见 SNP 占日本人群精神分裂症遗传风险的很大比例。