Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Transl Psychiatry. 2019 Aug 27;9(1):205. doi: 10.1038/s41398-019-0532-4.
Over 3000 candidate gene association studies have been performed to elucidate the genetic underpinnings of schizophrenia. However, a comprehensive evaluation of these studies' findings has not been undertaken since the decommissioning of the schizophrenia gene (SzGene) database in 2011. As such, we systematically identified and carried out random-effects meta-analyses for all polymorphisms with four or more independent studies in schizophrenia along with a series of expanded meta-analyses incorporating published and unpublished genome-wide association (GWA) study data. Based on 550 meta-analyses, 11 SNPs in eight linkage disequilibrium (LD) independent loci showed Bonferroni-significant associations with schizophrenia. Expanded meta-analyses identified an additional 10 SNPs, for a total of 21 Bonferroni-significant SNPs in 14 LD-independent loci. Three of these loci (MTHFR, DAOA, ARVCF) had never been implicated by a schizophrenia GWA study. In sum, the present study has provided a comprehensive summary of the current schizophrenia genetics knowledgebase and has made available all the collected data as a resource for the research community.
已经进行了超过 3000 项候选基因关联研究，以阐明精神分裂症的遗传基础。然而，自 2011 年精神分裂症基因 (SzGene) 数据库退役以来，尚未对这些研究结果进行全面评估。因此，我们系统地确定并对所有具有四个或更多独立研究的精神分裂症相关多态性进行了随机效应荟萃分析，同时还进行了一系列包含已发表和未发表全基因组关联 (GWA) 研究数据的扩展荟萃分析。基于 550 项荟萃分析，在 8 个连锁不平衡 (LD) 独立位点中的 11 个 SNP 与精神分裂症呈 Bonferroni 显著相关。扩展荟萃分析确定了另外 10 个 SNP，总计在 14 个 LD 独立位点中有 21 个 Bonferroni 显著 SNP。其中三个位点（MTHFR、DAOA、ARVCF）从未被精神分裂症 GWA 研究所涉及。总之，本研究全面总结了当前的精神分裂症遗传学知识库，并提供了所有收集的数据作为研究社区的资源。
