Allen Nicole C, Bagade Sachin, McQueen Matthew B, Ioannidis John P A, Kavvoura Fotini K, Khoury Muin J, Tanzi Rudolph E, Bertram Lars
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Nat Genet. 2008 Jul;40(7):827-34. doi: 10.1038/ng.171.
In an effort to pinpoint potential genetic risk factors for schizophrenia, research groups worldwide have published over 1,000 genetic association studies with largely inconsistent results. To facilitate the interpretation of these findings, we have created a regularly updated online database of all published genetic association studies for schizophrenia ('SzGene'). For all polymorphisms having genotype data available in at least four independent case-control samples, we systematically carried out random-effects meta-analyses using allelic contrasts. Across 118 meta-analyses, a total of 24 genetic variants in 16 different genes (APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53 and TPH1) showed nominally significant effects with average summary odds ratios of approximately 1.23. Seven of these variants had not been previously meta-analyzed. According to recently proposed criteria for the assessment of cumulative evidence in genetic association studies, four of the significant results can be characterized as showing 'strong' epidemiological credibility. Our project represents the first comprehensive online resource for systematically synthesized and graded evidence of genetic association studies in schizophrenia. As such, it could serve as a model for field synopses of genetic associations in other common and genetically complex disorders.
为了找出精神分裂症潜在的遗传风险因素，全球研究团队已发表了1000多项基因关联研究，但结果大多不一致。为便于解读这些研究结果，我们创建了一个定期更新的在线数据库，收录所有已发表的精神分裂症基因关联研究（“SzGene”）。对于在至少四个独立病例对照样本中具备基因型数据的所有多态性，我们使用等位基因对比系统地进行了随机效应荟萃分析。在118项荟萃分析中，16个不同基因（APOE、COMT、DAO、DRD1、DRD2、DRD4、DTNBP1、GABRB2、GRIN2B、HP、IL1B、MTHFR、PLXNA2、SLC6A4、TP53和TPH1）中的总共24个基因变异显示出名义上的显著效应，平均汇总比值比约为1.23。其中七个变异此前未进行过荟萃分析。根据最近提出的基因关联研究累积证据评估标准，四项显著结果可被认定为具有“强”流行病学可信度。我们的项目是首个全面的在线资源，用于系统综合和分级精神分裂症基因关联研究的证据。因此，它可为其他常见和基因复杂疾病的基因关联领域综述提供范例。
