Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
Mol Psychiatry. 2013 Jul;18(7):799-805. doi: 10.1038/mp.2012.76. Epub 2012 Jun 5.
Twin studies indicate that obsessive-compulsive disorder (OCD) is strongly influenced by additive genetic factors. Yet, molecular genetic association studies have yielded inconsistent results, possibly because of differences across studies in statistical power. Meta-analysis can yield greater power. This study reports the first comprehensive meta-analysis of the relationship between OCD and all previously examined polymorphisms for which there was sufficient information in the source studies to compute odds ratios (ORs). A total of 230 polymorphisms from 113 genetic association studies were identified. A full meta-analysis was conducted for 20 polymorphisms that were examined in 5 or more data sets, and a secondary meta-analysis (limited to the computation of mean effect sizes) was conducted for 210 polymorphisms that were examined in fewer than 5 data sets. In the main meta-analysis, OCD was associated with serotonin-related polymorphisms (5-HTTLPR and HTR2A) and, in males only, with polymorphisms involved in catecholamine modulation (COMT and MAOA). Nonsignificant trends were identified for two dopamine-related polymorphisms (DAT1 and DRD3) and a glutamate-related polymorphism (rs3087879). The secondary meta-analysis identified another 18 polymorphisms with significant ORs that merit further investigation. This study demonstrates that OCD is associated with multiple genes, with most having a modest association with OCD. This suggests a polygenic model of OCD, consistent with twin studies, in which multiple genes make small, incremental contributions to the risk of developing the disorder. Future studies, with sufficient power to detect small effects, are needed to investigate the genetic basis of OCD subtypes, such as early vs late onset OCD.
双生子研究表明，强迫症（OCD）受加性遗传因素的强烈影响。然而，分子遗传关联研究得出的结果并不一致，这可能是由于不同研究在统计能力上存在差异。荟萃分析可以提高效能。本研究报告了 OCD 与所有先前检查的多态性之间关系的首次全面荟萃分析，这些多态性在源研究中有足够的信息来计算优势比（OR）。从 113 项遗传关联研究中确定了 230 个多态性。对 20 个在 5 个或更多数据集进行检查的多态性进行了全面荟萃分析，对在少于 5 个数据集进行检查的 210 个多态性进行了二级荟萃分析（仅限于计算平均效应大小）。在主要的荟萃分析中，OCD 与与 5-羟色胺相关的多态性（5-HTTLPR 和 HTR2A）有关，仅在男性中与涉及儿茶酚胺调节的多态性（COMT 和 MAOA）有关。两个与多巴胺相关的多态性（DAT1 和 DRD3）和一个与谷氨酸相关的多态性（rs3087879）有非显著趋势。二级荟萃分析还确定了另外 18 个具有显著 OR 的多态性，这些多态性值得进一步研究。本研究表明，OCD 与多个基因有关，大多数基因与 OCD 有轻微的关联。这表明 OCD 是一种多基因模型，与双胞胎研究一致，即多个基因对发病风险的微小、渐进性贡献。需要进行具有足够效能来检测小效应的未来研究，以研究 OCD 亚型（如早发性和晚发性 OCD）的遗传基础。
