Farrell M S, Werge T, Sklar P, Owen M J, Ophoff R A, O'Donovan M C, Corvin A, Cichon S, Sullivan P F
Center for Psychiatric Genomics, Department of Genetics, Genomic Medicine, University of North Carolina, Chapel Hill, NC, USA.
1] Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Denmark [2] Department of Clinical Medicine, University of Copenhagen, Copenhagen, Aarhus, Denmark [3] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Mol Psychiatry. 2015 May;20(5):555-62. doi: 10.1038/mp.2015.16. Epub 2015 Mar 10.
Prior to the genome-wide association era, candidate gene studies were a major approach in schizophrenia genetics. In this invited review, we consider the current status of 25 historical candidate genes for schizophrenia (for example, COMT, DISC1, DTNBP1 and NRG1). The initial study for 24 of these genes explicitly evaluated common variant hypotheses about schizophrenia. Our evaluation included a meta-analysis of the candidate gene literature, incorporation of the results of the largest genomic study yet published for schizophrenia, ratings from informed researchers who have published on these genes, and ratings from 24 schizophrenia geneticists. On the basis of current empirical evidence and mostly consensual assessments of informed opinion, it appears that the historical candidate gene literature did not yield clear insights into the genetic basis of schizophrenia. A likely reason why historical candidate gene studies did not achieve their primary aims is inadequate statistical power. However, the considerable efforts embodied in these early studies unquestionably set the stage for current successes in genomic approaches to schizophrenia.
在全基因组关联研究时代之前，候选基因研究是精神分裂症遗传学的主要方法。在这篇特邀综述中，我们探讨了25个精神分裂症历史候选基因（例如，儿茶酚-O-甲基转移酶基因、精神分裂症相关1基因、dysbindin-1基因和神经调节蛋白1基因）的现状。其中24个基因的初始研究明确评估了关于精神分裂症的常见变异假说。我们的评估包括对候选基因文献的荟萃分析、纳入迄今发表的关于精神分裂症的最大规模基因组研究结果、已发表这些基因相关研究的资深研究人员的评分以及24位精神分裂症遗传学家的评分。基于当前的实证证据以及大多达成共识的专家意见评估，历史候选基因文献似乎并未对精神分裂症的遗传基础提供清晰的见解。历史候选基因研究未能实现其主要目标的一个可能原因是统计效力不足。然而，这些早期研究中所付出的巨大努力无疑为当前精神分裂症基因组学方法的成功奠定了基础。
