Bertram Lars
Genetics and Aging Research Unit, MGH-East (MassGeneral Institute for Neurodegenerative Disease), Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Schizophr Bull. 2008 Sep;34(5):806-12. doi: 10.1093/schbul/sbn079. Epub 2008 Jul 21.
Genetically, schizophrenia is a complex disease whose pathogenesis is likely governed by a number of different risk factors. While substantial efforts have been made to identify the underlying susceptibility alleles over the past 2 decades, they have been of only limited success. Each year, the field is enriched with nearly 150 additional genetic association studies, each of which either proposes or refutes the existence of certain schizophrenia genes. To facilitate the evaluation and interpretation of these findings, we have recently created a database for genetic association studies in schizophrenia ("SzGene"; available at http://www.szgene.org). In addition to systematically screening the scientific literature for eligible studies, SzGene also reports the results of allele-based meta-analyses for polymorphisms with sufficient genotype data. Currently, these meta-analyses highlight not only over 20 different potential schizophrenia genes, many of which represent the "usual suspects" (eg, various dopamine receptors and neuregulin 1), but also several that were never meta-analyzed previously. All the highlighted loci contain at least one variant showing modest (summary odds ratios approximately 1.20 [range 1.06-1.45]) but nominally significant risk effects. This review discusses some of the strengths and limitations of the SzGene database, which could become a useful bioinformatics tool within the schizophrenia research community.
从基因角度来看,精神分裂症是一种复杂疾病,其发病机制可能受多种不同风险因素的控制。在过去20年里,人们为确定潜在的易感等位基因付出了巨大努力,但成效有限。每年,该领域都会新增近150项基因关联研究,每项研究都在提出或反驳某些精神分裂症基因的存在。为便于对这些研究结果进行评估和解读,我们最近创建了一个精神分裂症基因关联研究数据库(“SzGene”;可在http://www.szgene.org获取)。除了系统筛选科学文献以寻找符合条件的研究外,SzGene还报告了针对具有足够基因型数据的多态性进行的基于等位基因的荟萃分析结果。目前,这些荟萃分析不仅突出了20多种不同的潜在精神分裂症基因,其中许多是“常见嫌疑基因”(例如,各种多巴胺受体和神经调节蛋白1),还包括一些此前从未进行过荟萃分析的基因。所有突出显示的基因座都至少包含一个显示适度(汇总比值比约为1.20 [范围1.06 - 1.45])但具有名义上显著风险效应的变异。本综述讨论了SzGene数据库的一些优点和局限性,该数据库可能成为精神分裂症研究领域中一个有用的生物信息学工具。