Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database
Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database
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DOI：
10.1038/ng.171
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发表时间：
2008-07-01
期刊：
影响因子：
30.8
通讯作者：
Bertram, Lars
中科院分区：
文献类型：
--
作者：
Allen, Nicole C.;Bagade, Sachin;Bertram, Lars
为了确定精神分裂症的潜在遗传风险因素，世界各地的研究小组已经发表了1,000多项遗传关联研究，结果基本上不一致。为了便于解释这些发现，我们创建了一个定期更新的在线数据库，其中包含所有已发表的精神分裂症遗传关联研究（“SzGene”）。对于至少有四个独立的病例对照样本的基因型数据的所有多态性，我们系统地进行了随机效应的荟萃分析，使用等位基因的对比。在118项荟萃分析中，16个不同基因（APOE、COMT、DAO、DRD 1、DRD 2、DRD 4、DTNBP 1、GABRB 2、GRIN 2B、HP、IL 1B、MTHFR、PLXNA 2、SLC 6A 4、TP 53和TPH 1）的24种遗传变异显示出名义上的显著影响，平均汇总比值比接近1.23。其中7个变体之前未进行荟萃分析。根据最近提出的评估遗传关联研究中累积证据的标准，其中四个重要结果可以被描述为显示出“强大的”流行病学可信度。我们的项目代表了第一个全面的在线资源，用于精神分裂症遗传关联研究的系统综合和分级证据。因此，它可以作为一个模型，在其他常见的和遗传复杂的疾病的遗传协会现场概要。
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 similar to 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.