Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.
Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.
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DOI：
10.1176/appi.ajp.2012.12020237
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发表时间：
2013-02
影响因子：
17.7
通讯作者：
Uher, Rudolf
中科院分区：
文献类型：
--
作者：
Uher, Rudolf
间接证据表明，常见的遗传变异有助于抑郁症患者抗抑郁疗效的个体差异，但以前的研究可能没有足够的动力来检测这些影响。对三项全基因组药物遗传学研究的数据进行了荟萃分析，（基于基因组的抑郁症治疗药物[GENDEP]项目、慕尼黑抗抑郁反应特征[MARS]项目和缓解抑郁症的序贯治疗替代方案[星星 *D]研究），其中包括2，256名患有重度抑郁症的北方欧洲血统的个体，并前瞻性收集抗抑郁药治疗结果。插补后，对120万个单核苷酸多态性进行了检测，捕获了与长达12周的抗抑郁药治疗后症状改善和缓解相关的常见变异。在主要分析中，没有个体关联达到全基因组统计学显著性阈值。来自GENDEP和MARS参与者荟萃分析的多基因评分占星星 *D结果方差的约1.2%，表明分布在许多多态性上的弱一致信号。一项仅限于1,354名接受西酞普兰（星星 *D）或艾司西酞普兰（GENDEP）治疗的个体的分析发现，5号染色体上的一个基因间区域与治疗2周后的早期改善相关。尽管荟萃分析的统计功效增加，但作者没有发现抗抑郁药治疗结果的可靠预测因素，尽管他们确实发现了普通遗传变异导致抗抑郁药反应个体差异的适度直接证据。
Indirect evidence suggests that common genetic variation contributes to individual differences in antidepressant efficacy among individuals with major depressive disorder, but previous studies may have been underpowered to detect these effects. A meta-analysis was performed on data from three genome-wide pharmacogenetic studies (the Genome-Based Therapeutic Drugs for Depression [GENDEP] project, the Munich Antidepressant Response Signature [MARS] project, and the Sequenced Treatment Alternatives to Relieve Depression [STAR*D] study), which included 2,256 individuals of Northern European descent with major depressive disorder, and antidepressant treatment outcomes were prospectively collected. After imputation, 1.2 million single-nucleotide polymorphisms were tested, capturing common variation for association with symptomatic improvement and remission after up to 12 weeks of antidepressant treatment. No individual association met a genome-wide threshold for statistical significance in the primary analyses. A polygenic score derived from a meta-analysis of GENDEP and MARS participants accounted for up to approximately 1.2% of the variance in outcomes in STAR*D, suggesting a weakly concordant signal distributed over many polymorphisms. An analysis restricted to 1,354 individuals treated with citalopram (STAR*D) or escitalopram (GENDEP) identified an intergenic region on chromosome 5 associated with early improvement after 2 weeks of treatment. Despite increased statistical power accorded by meta-analysis, the authors identified no reliable predictors of antidepressant treatment outcome, although they did identify modest, direct evidence that common genetic variation contributes to individual differences in antidepressant response.
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DOI：
10.1007/s12265-010-9178-6
发表时间：
2010-06-01
影响因子：
3.4
作者：
Roberts, Robert;Wells, George A.;Chen, Li
通讯作者：
Chen, Li
影响因子：
4.8
作者：
Franchini, L;Serretti, A;Smeraldi, E
通讯作者：
Smeraldi, E
影响因子：
4.8
作者：
Hennings, Johannes M.;Owashi, Toshimi;Lucae, Susanne
通讯作者：
Lucae, Susanne
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick
影响因子：
2.1
作者：
Lin, D. Y.;Zeng, D.
通讯作者：
Zeng, D.