Failure to find an association between myosin heavy chain 9, non-muscle (MYH9) and schizophrenia: A three-stage case–control association study
Failure to find an association between myosin heavy chain 9, non-muscle (MYH9) and schizophrenia: A three-stage case–control association study
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DOI：
10.1016/j.schres.2010.01.023
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发表时间：
2010-05
影响因子：
4.5
通讯作者：
Hideki Amagane;Yuichiro Watanabe;N. Kaneko;A. Nunokawa;T. Muratake;H. Ishiguro;T. Arinami;H. Ujike;T. Inada;N. Iwata;H. Kunugi;Tsukasa Sasaki;R. Hashimoto;M. Itokawa;N. Ozaki;T. Someya
中科院分区：
文献类型：
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作者：
Hideki Amagane;Yuichiro Watanabe;N. Kaneko;A. Nunokawa;T. Muratake;H. Ishiguro;T. Arinami;H. Ujike;T. Inada;N. Iwata;H. Kunugi;Tsukasa Sasaki;R. Hashimoto;M. Itokawa;N. Ozaki;T. Someya
几项全基因组连锁研究表明 22 号染色体长臂上的标记与精神分裂症之间存在联系。另据报道，22q11.2 缺失会增加患精神分裂症的风险。因此，22q是精神分裂症的候选区域。为了寻找 22q 上精神分裂症的遗传易感位点，我们在日本个体中进行了一项三阶段病例对照关联研究。在第一阶段，我们检查了 766 名个体（340 名精神分裂症患者和 426 名对照个体）22q 上的 13 个微卫星标记，发现 AFM262VH5 (D22S283) 与精神分裂症存在潜在关联。在第二阶段，我们使用 25 个标记单核苷酸多态性 (SNP) 对 AFM262VH5 所在的肌球蛋白重链 9 非肌肉 (MYH9) 基因进行了精细定位。我们在 1193 名个体（595 名患者和 598 名对照者）中获得了 MYH9 中的三个 SNP 与精神分裂症之间的潜在关联，其中包括第一阶段分析的个体。然而，在第三阶段，我们无法在 4694 名独立个体（2288 名患者和 2406 名对照者）中复制这些关联。我们的结果表明，MYH9 不会增加日本人群对精神分裂症的易感性，尽管我们不能排除 22q 上其他基因对精神分裂症发病机制的可能贡献。
Several genome-wide linkage studies have suggested linkage between markers on the long arm of chromosome 22 and schizophrenia. It has also been reported that 22q11.2 deletions increase the risk of schizophrenia. Therefore, 22q is a candidate region for schizophrenia. To search for genetic susceptibility loci for schizophrenia on 22q, we conducted a three-stage case–control association study in Japanese individuals. In the first stage, we examined 13 microsatellite markers on 22q in 766 individuals (340 patients with schizophrenia and 426 control individuals) and found a potential association of AFM262VH5 (D22S283) with schizophrenia. In the second stage, we performed fine mapping of the myosin heavy chain 9, non-muscle (MYH9) gene, where AFM262VH5 is located, using 25 tagging single nucleotide polymorphisms (SNPs). We obtained potential associations between three SNPs in MYH9 and schizophrenia in 1193 individuals (595 patients and 598 controls), which included the individuals analyzed in the first stage. In the third stage, however, we could not replicate these associations in 4694 independent individuals (2288 patients and 2406 controls). Our results suggest that MYH9 does not confer increased susceptibility to schizophrenia in the Japanese population, although we could not exclude possible contributions of other genes on 22q to the pathogenesis of schizophrenia.