A genome-wide association study of a sustained pattern of antidepressant response.
A genome-wide association study of a sustained pattern of antidepressant response.
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DOI：
10.1016/j.jpsychires.2013.05.002
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发表时间：
2013-09
影响因子：
4.8
通讯作者：
Hamilton, Steven P.
中科院分区：
文献类型：
--
作者：
Hunter, Aimee M.;Leuchter, Andrew F.;Power, Robert A.;Muthen, Bengt;McGrath, Patrick J.;Lewis, Cathryn M.;Cook, Ian A.;Garriock, Holly A.;McGuffin, Peter;Uher, Rudolf;Hamilton, Steven P.
全基因组关联研究未能复制使用单一终点定义的与抗抑郁药物反应相关的常见遗传变异。基因影响可以通过检查持续和非持续反应模式之间的个体差异来辨别，这可能会区分药物效果和非特异性，或者对积极药物的安慰剂反应。我们在1,116名患有严重抑郁障碍的患者中进行了一项GWAS试验，这些患者来自缓解抑郁的序贯治疗替代疗法(STAR*D)试验，这些患者使用生长混合建模显示了西酞普兰治疗12周后的持续和非持续的临床反应模式。重复分析检查了585名来自基于基因组的抑郁症治疗药物(GENDEP)试验的受试者。与STAR*D持续反应相关最强的是酰辅酶A合成酶短链家族成员3基因内的单核苷酸多态(SNP；rs10492002)(ACSS3，p值=4.5×10-6，优势比=0.61)。没有一个SNP达到我们的全基因组意义的门槛。在STAR*D的前25个SNP中，有18个的SNP数据在GENDEP中可用。最具重复性的关联是与SNP rs7816924(p=0.008，OR=1.58)；没有SNP达到复制p值0.003的阈值。对这18个SNP的联合分析发现，最强的信号来自rs7816924(p=2.11×10-7)，它位于硫酸软骨素N-乙酰氨基半乳糖转移酶1基因(CSGALNACT1)。一项探索性遗传通路分析显示，有证据表明KEGG通路参与了长时程增强(FDR=0.02)。结果表明，持续反应与新的基因关联。
Genome-wide association studies (GWAS) have failed to replicate common genetic variants associated with antidepressant response, as defined using a single endpoint. Genetic influences may be discernible by examining individual variation between sustained versus unsustained patterns of response, which may distinguish medication effects from non-specific, or placebo responses to active medication. We conducted a GWAS among 1,116 subjects with Major Depressive Disorder from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who were characterized using Growth Mixture Modeling as showing a sustained versus unsustained pattern of clinical response over 12 weeks of treatment with citalopram. Replication analyses examined 585 subjects from the Genome-based Therapeutic Drugs for Depression (GENDEP) trial. The strongest association with sustained as opposed to unsustained response in STAR*D involved a single nucleotide polymorphism (SNP; rs10492002) within the acyl-CoA synthetase short-chain family member 3 gene (ACSS3, p-value = 4.5 × 10-6, odds ratio = 0.61). No SNPs met our threshold for genome-wide significance. SNP data were available in GENDEP for 18 of the top 25 SNPs in STAR*D. The most replicable association was with SNP rs7816924 (p = 0.008, OR = 1.58); no SNP met the replication p-value threshold of 0.003. Joint analysis of these 18 SNPs resulted in the strongest signal coming from rs7816924 (p = 2.11 × 10-7), which resides in chondroitin sulfate N-acetylgalactosaminyltransferase 1 gene (CSGALNACT1). An exploratory genetic pathway analysis revealed evidence for an involvement of the KEGG pathway of long-term potentiation (FDR =.02). Results suggest novel genetic associations to sustained response.
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影响因子：
7
作者：
Muthen, Bengt;Asparouhov, Tihomir;Hunter, Aimee M.;Leuchter, Andrew F.
通讯作者：
Leuchter, Andrew F.
影响因子：
9.8
作者：
Liu, Jimmy Z.;Mcrae, Allan F.;Macgregor, Stuart
通讯作者：
Macgregor, Stuart
DOI：
10.1017/s1461145711001891
发表时间：
2012-11-01
影响因子：
4.8
作者：
Kao, Chung-Feng;Jia, Peilin;Kuo, Po-Hsiu
通讯作者：
Kuo, Po-Hsiu
影响因子：
11
作者：
Malhotra, A. K.;Zhang, J-P;Lencz, T.
通讯作者：
Lencz, T.
影响因子：
1.9
作者：
Muthén, B;Shedden, K
通讯作者：
Shedden, K