Neuroscience Graduate Program, McMaster University, 1280 Main Street West, Ontario L8S 4L8, Canada; Women's Health Concerns Clinic, St. Joseph's Healthcare, 100 West 5(th) Street, Hamilton, Ontario L8N 3K7, Canada.
Department of Psychiatry and Behavioural Neurosciences, McMaster University, 1280 Main Street West, Ontario L8S 4L8, Canada.
J Affect Disord. 2020 Oct 1;275:278-289. doi: 10.1016/j.jad.2020.06.016. Epub 2020 Jun 23.
Genetic risk factors that contribute to obsessive-compulsive disorder (OCD) have yet to be elucidated. Historically, serotonergic dysfunction has been implicated. Evidence from the literature points towards the serotonin receptor 2A gene (HTR2A) as a primary candidate. Our meta-analysis investigated whether polymorphisms in HTR2A are associated with OCD or its subtypes, based on sex and age of onset.
Studies employing case-control or family-based designs were systematically searched, and those meeting eligibility underwent quality assessment, resulting in 18 studies. A random-effects meta-analysis using standard inverse-variance weighting to compute odds ratio (OR) was conducted. To examine sensitivity, results were also obtained using a more conservative statistical method.
Three HTR2A variants were identified: T102C, G-1438A, and C516T. T102C and G-1438A were analyzed together due to strong linkage disequilibrium, where the 102T allele co-occurs with -1438A allele. Results reported as OR [95%CI] showed that the T/A allele were significantly associated with OCD, 1.14 [1.01, 1.29]. After stratification, results remained significant for females, 1.20 [1.00, 1.45], and early-onset OCD, 1.27 [1.02, 1.58], but not males, 1.06 [0.91, 1.23]. No associations were found for late-onset OCD, 0.98 [0.70, 1.37], or C516T, 1.22 [0.14, 10.37], but conclusions cannot be drawn from two studies.
Associations no longer reached significance with the conservative statistical approach. HTR2A alone cannot explain OCD complexity and limited samples reporting genetic data according to subtypes.
These results suggest a possible association of HTR2A polymorphisms with OCD, but further investigations considering sex and age of onset with larger samples is needed.
导致强迫症（OCD）的遗传风险因素尚未阐明。历史上，已涉及到血清素能功能障碍。文献中的证据表明，5-羟色胺受体 2A 基因（HTR2A）是主要候选基因。我们的荟萃分析根据发病年龄和性别，研究了 HTR2A 多态性是否与 OCD 或其亚型有关。
系统搜索了采用病例对照或家系设计的研究，并对符合条件的研究进行了质量评估，最终纳入了 18 项研究。使用标准逆方差加权计算比值比（OR）的随机效应荟萃分析。为了检查敏感性，还使用更保守的统计方法获得了结果。
确定了三种 HTR2A 变体：T102C、G-1438A 和 C516T。由于强连锁不平衡，T102C 和 G-1438A 一起进行了分析，其中 102T 等位基因与-1438A 等位基因共同出现。报告为 OR [95%CI] 的结果表明，T/A 等位基因与 OCD 显著相关，1.14 [1.01, 1.29]。分层后，结果在女性中仍然显著，1.20 [1.00, 1.45]，和早发性 OCD 中显著，1.27 [1.02, 1.58]，但在男性中不显著，1.06 [0.91, 1.23]。未发现晚发性 OCD 或 C516T 存在相关性，分别为 0.98 [0.70, 1.37] 和 1.22 [0.14, 10.37]，但由于两项研究的报告结果，无法得出结论。
使用保守的统计方法，关联不再具有统计学意义。仅 HTR2A 不能解释 OCD 的复杂性，并且报告遗传数据的样本有限，根据亚型进行了报告。
这些结果表明 HTR2A 多态性与 OCD 可能存在关联，但需要进一步进行考虑性别和发病年龄，并纳入更大样本的研究。
