A highly significant association between a COMT haplotype and schizophrenia
A highly significant association between a COMT haplotype and schizophrenia
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DOI：
10.1086/344514
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发表时间：
2002-12-01
影响因子：
9.8
通讯作者：
Darvasi, A
中科院分区：
文献类型：
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作者：
Shifman, S;Bronstein, M;Darvasi, A
多项证据表明，儿茶酚-O-甲基转移酶（COMT）基因是精神分裂症的候选基因。其中之一是它在儿茶酚胺神经递质代谢中的生化功能；另一个是染色体 22q11 上的微缺失，其中包含 COMT 基因并导致腭心面综合征，这是一种与精神病（尤其是精神分裂症）高发病率相关的综合征。人们对 COMT 基因作为精神分裂症候选危险因素的兴趣导致了许多连锁和关联分析。然而，这些都未能产生任何结论性的结果。在这里，我们报告了一种有效的基因发现方法。该方法包括（i）大样本量——据我们所知，本研究是迄今为止在精神分裂症中进行的最大的病例对照研究； (ii) 使用德系犹太人，这是一个明确定义的同质群体； (iii) 逐步程序，其中扫描 DNA 池中的几个单核苷酸多态性 (SNP)，然后对相关 SNP 进行个体基因分型和单倍型分析。我们发现精神分裂症和 COMT 单倍型之间存在高度显着的关联 (P = 9.5 x 10(-8))。该方法可广泛应用于其他常见疾病的基因解析。
Several lines of evidence have placed the catechol-O-methyltransferase (COMT) gene in the limelight as a candidate gene for schizophrenia. One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia. The interest in the COMT gene as a candidate risk factor for schizophrenia has led to numerous linkage and association analyses. These, however, have failed to produce any conclusive result. Here we report an efficient approach to gene discovery. The approach consists of (i) a large sample size-to our knowledge, the present study is the largest case-control study performed to date in schizophrenia; (ii) the use of Ashkenazi Jews, a well defined homogeneous population; and (iii) a stepwise procedure in which several single nucleotide polymorphisms (SNPs) are scanned in DNA pools, followed by individual genotyping and haplotype analysis of the relevant SNPs. We found a highly significant association between schizophrenia and a COMT haplotype (P = 9.5 x 10(-8)). The approach presented can be widely implemented for the genetic dissection of other common diseases.