Genome-wide association study of SSRI/SNRI-induced sexual dysfunction in a Japanese cohort with major depression
Genome-wide association study of SSRI/SNRI-induced sexual dysfunction in a Japanese cohort with major depression
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DOI：
10.1016/j.psychres.2012.01.023
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发表时间：
2012-08-15
影响因子：
11.3
通讯作者：
Saito, Yoshiro
中科院分区：
文献类型：
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作者：
Kurose, Kouichi;Hiratsuka, Kazuyuki;Saito, Yoshiro
性功能障碍是选择性血清素再摄取抑制剂（SSRI）和血清素去甲肾上腺素再摄取抑制剂（SNRI）的主要副作用。我们进行了一项全基因组关联研究，通过在 201 名日本重度抑郁症患者（其中 36 名患有由 SSRI（帕罗西汀或氟伏沙明）或 SNRI（米那普仑）诱发的性功能障碍）中检测 186 320 个单核苷酸多态性 (SNP) 标记，确定导致 SSRI/SNRI 诱发性功能障碍风险的遗传因素。 Cochran-Armitage 趋势检验显示，在错误发现率 (FDR) 校正后，紧密聚集在染色体 14q21.3 上不同区域的 11 个 SNP 与 SSRI/SNRI 诱导的性功能障碍在全基因组显着水平上相关，其中最强的 SNP 关联与 rs1160351 相关（P = 3.04 x 10(-7) 风险比 = 2.92, 95% 置信区间 (CI) = 1.79-4.76）。这些 SNP 定位到 MDGA2 基因的内含子区域。曼哈顿图显示，在多变量逻辑回归分析中调整性别和年龄后，MDGA2 中仍存在强关联峰，尽管 P 值略有增加且变得不显着。需要更大样本量的重复研究来验证这项探索性研究，但我们的研究结果可能为 SSRI/SNRI 引起的性功能障碍的遗传基础提供见解。 (C) 2012 Elsevier Ireland Ltd. 保留所有权利。
Sexual dysfunction is a major side effect of selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs). We conducted a genome-wide association study to identify the genetic factors contributing to the risk of SSRI/SNRI-induced sexual dysfunction by testing 186 320 single nucleotide polymorphism (SNP) markers in a cohort of 201 Japanese major depression patients including 36 with sexual dysfunction induced by SSRI (paroxetine or fluvoxamine) or SNRI (milnacipran). The Cochran-Armitage trend test showed that 11 SNPs, tightly clustered in a distinct region on chromosome 14q21.3, were associated with SSRI/SNRI-induced sexual dysfunction at a genome-wide significance level after false discovery rate (FDR) correction, and the strongest SNP association was with rs1160351 (P = 3.04 x 10(-7) risk ratio = 2.92, 95% confidence interval (CI) = 1.79-4.76). These SNPs mapped to the intronic region of the MDGA2 gene. A Manhattan plot showed that the strong association peak remained in MDGA2 after adjustment for sex and age in a multivariable logistic regression analysis although P values increased slightly and became non-significant. Replication studies with larger sample sizes are required to validate this exploratory study, but our findings may provide insights into the genetic basis of sexual dysfunction induced by SSRI/SNRI. (C) 2012 Elsevier Ireland Ltd. All rights reserved.