No support for replication of the genetic variants identified by a recent mega-analysis of the treatment response to antidepressants
No support for replication of the genetic variants identified by a recent mega-analysis of the treatment response to antidepressants
复制标题
不支持最近对抗抑郁药治疗反应的大型分析所确定的遗传变异的复制
DOI：
10.1038/jhg.2015.21
复制
发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Iwata N
中科院分区：
文献类型：
--
作者：
Hatano M;Ikeda M;Kondo K;Saito T;Shimasaki A;Esaki K;Umene-Nakano W;Yoshimura R;Nakamura J;Ozaki N;Iwata N
抗抑郁药是重度抑郁症（MDD）患者最常用的治疗方法。然而，缓解率是不够的;大约三分之一服用这些药物的患者被认为是“治疗抵抗”。1此外，反应不佳或延迟找到合适的药物对治疗效果有负面影响。因此，一个有用的预测治疗反应是必要的，在临床环境中，最好的方法之一是药物遗传学/药物基因组学（PGt/PGx）。尽管大量经典的PGt研究都以候选基因为靶点，但迄今为止还没有一致的结果。最近，为了在全基因组水平上调查遗传变异，已经进行了三项PGx研究（GENDEP、2 MARS 3和星星 * D4）。所有这些，以及他们的大分析，5再次显示没有单核苷酸多态性（SNP）与全基因组的意义（P= 5× 10− 8）.从大规模分析的结果来看，5在样本量最大化的情况下，具有适度关联的SNP的效应量不是非常大（比值比（OR），~ 1.5），虽然PGt/PGx表型被认为有更大的影响大小相比，复杂的疾病。因此，由于复制分析对于避免II型错误至关重要，因此我们有动机使用日本人群进行这项复制研究。本研究检查了217例日裔MDD患者（男性= 114例，女性= 103例，平均年龄±sd= 47.1±15.0岁）。所有受试者均接受选择性5-羟色胺转运体再摄取抑制剂（SSRI）单药治疗8周
Antidepressants are the most commonly used treatment for patients with major depressive disorder (MDD). The remission rate, however, is insufficient; approximately one-third of patients taking these medications are considered to be ‘treatment resistant’. 1 In addition, poor response or delay in finding an appropriate drug has a negative impact on the therapeutic effect. Therefore, a useful predictor for the treatment response is warranted in the clinical setting, and one of the best approaches is the pharmacogenetics/pharmacogenomics (PGt/PGx). Although a large number of classical PGt studies have targeted candidate genes, there are no consistent results till date. Recently, to survey genetic variants at the genome-wide level, three PGx studies (GENDEP, 2 MARS3 and STAR* D4) have been conducted. All of these, as well as their mega-analysis, 5 again revealed no single-nucleotide polymorphisms (SNPs) with genome-wide significance (P= 5× 10− 8).From the results of the mega-analysis, 5 where the sample size was maximized, the effect size of the SNPs with modest association was not extremely large (odds ratio (OR),~ 1.5), although PGt/PGx phenotypes were presumed to have a larger effect size compared with that of complex diseases. Therefore, as the replication analysis is essential to avoid type II errors, we were motivated to conduct this replication study using a Japanese population. Two-hundred and seventeen patients with MDD who were of Japanese ancestry were examined (males= 114, females= 103, mean age±sd= 47.1±15.0 years) in this study. All the subjects were treated by selective serotonin transporter reuptake inhibitor (SSRI) monotherapy for 8 weeks