Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, Antwerp, Belgium.
Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1240-3. doi: 10.1002/ajmg.b.31088.
Previous studies implicated centrosomal dysfunction as a source of various neuropsychiatric disorders, including schizophrenia (SZ). Two recent reports [Gurling et al., 2006; Datta et al., 2008. Mol Psychiatry] described an association between polymorphisms in the PCM1 gene and SZ in a UK/Scottish population. In this study, we aimed to replicate these findings in a Northern Swedish association sample of 486 research subjects with SZ and 512 unrelated control individuals. We genotyped 12 previously described SNP markers and carried out haplotype analyses using the same multi-marker haplotypes previously reported. Though we could not replicate the association with SNPs rs445422 and rs208747, we did observe a significant protective association with intronic SNP rs13276297. Furthermore, we performed a meta-analysis comprising 1,794 SZ patients and 1,553 controls, which confirmed the previously reported association with rs445422 and rs208747. These data provide further evidence that PCM1-though certainly not a major risk factor in the Northern Swedish population-cannot be ruled out as a contributor to SZ risk and/or protection, and deserves further replication in larger populations to elucidate its role in disease etiology.
先前的研究表明,中心体功能障碍是各种神经精神疾病(包括精神分裂症)的根源之一。最近有两项研究[Gurling 等人,2006 年;Datta 等人,2008 年。分子精神病学]描述了 PCM1 基因多态性与英国/苏格兰人群精神分裂症之间的关联。在这项研究中,我们旨在对来自瑞典北部的 486 名精神分裂症患者和 512 名无关对照者的关联样本中复制这些发现。我们对 12 个先前描述的 SNP 标记进行了基因分型,并使用先前报道的相同多标记单体型进行了单体型分析。尽管我们无法复制与 SNP rs445422 和 rs208747 的关联,但我们确实观察到与内含子 SNP rs13276297 存在显著的保护性关联。此外,我们进行了一项包含 1794 名精神分裂症患者和 1553 名对照者的荟萃分析,该分析证实了先前报道的与 rs445422 和 rs208747 的关联。这些数据进一步证明,PCM1 尽管在瑞典北部人群中肯定不是主要的风险因素,但不能排除其对精神分裂症风险和/或保护的贡献,并且值得在更大的人群中进一步复制,以阐明其在疾病病因学中的作用。