Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
J Hum Genet. 2009 Feb;54(2):98-107. doi: 10.1038/jhg.2008.14. Epub 2009 Jan 16.
The development of molecular psychiatry in the last few decades identified a number of candidate genes that could be associated with schizophrenia. A great number of studies often result with controversial and non-conclusive outputs. However, it was determined that each of the implicated candidates would independently have a minor effect on the susceptibility to that disease. Herein we report results from our replication study for association using 255 Bulgarian patients with schizophrenia and schizoaffective disorder and 556 Bulgarian healthy controls. We have selected from the literatures 202 single nucleotide polymorphisms (SNPs) in 59 candidate genes, which previously were implicated in disease susceptibility, and we have genotyped them. Of the 183 SNPs successfully genotyped, only 1 SNP, rs6277 (C957T) in the DRD2 gene (P=0.0010, odds ratio=1.76), was considered to be significantly associated with schizophrenia after the replication study using independent sample sets. Our findings support one of the most widely considered hypotheses for schizophrenia etiology, the dopaminergic hypothesis.
过去几十年的分子精神病学发展确定了许多候选基因,这些基因可能与精神分裂症有关。大量的研究经常得出有争议和非结论性的结果。然而,研究表明,每个涉及的候选基因都会对该疾病的易感性产生独立的轻微影响。本文报告了我们使用 255 名保加利亚精神分裂症和分裂情感障碍患者和 556 名保加利亚健康对照进行关联研究的复制结果。我们从文献中选择了 59 个候选基因中的 202 个单核苷酸多态性(SNP),这些基因先前与疾病易感性有关,并且我们对它们进行了基因分型。在成功基因分型的 183 个 SNP 中,只有 DRD2 基因中的 rs6277(C957T)(P=0.0010,优势比=1.76)在使用独立样本集进行复制研究后被认为与精神分裂症显著相关。我们的研究结果支持了最广泛考虑的精神分裂症病因学假说之一,即多巴胺假说。