Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder.
Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder.
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DOI：
10.3389/fpsyt.2018.00065
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发表时间：
2018
影响因子：
4.7
通讯作者：
Baune BT
中科院分区：
文献类型：
--
作者：
Amare AT;Schubert KO;Tekola-Ayele F;Hsu YH;Sangkuhl K;Jenkins G;Whaley RM;Barman P;Batzler A;Altman RB;Arolt V;Brockmöller J;Chen CH;Domschke K;Hall-Flavin DK;Hong CJ;Illi A;Ji Y;Kampman O;Kinoshita T;Leinonen E;Liou YJ;Mushiroda T;Nonen S;Skime MK;Wang L;Kato M;Liu YL;Praphanphoj V;Stingl JC;Bobo WV;Tsai SJ;Kubo M;Klein TE;Weinshilboum RM;Biernacka JM;Baune BT
研究报告称，五大人格特征与重度抑郁症（MDD）之间存在很强的遗传相关性。此外，人格特征被认为与抗抑郁药物治疗的反应有关，这可能部分由遗传因素介导。在这项研究中，我们研究了来自五大人格特征的多基因评分（pgs）是否能预测服用选择性血清素再摄取抑制剂（SSRIs）的重度抑郁症患者的治疗反应和缓解。此外，我们对这些性状的全基因组关联研究（GWASs）进行了荟萃分析，以确定支持跨性状多基因关联的遗传变异。PGS分析使用来自两个队列的数据：药物基因组学研究网络抗抑郁药物药物基因组学研究（PGRN-AMPS, n = 529）和国际SSRI药物基因组学联盟（ISPC, n = 865）。结合GWAS对SSRIs治疗结果和人格特质的汇总统计进行跨特质GWAS荟萃分析。结果显示，在两个队列中，开放性和神经质的PGS与SSRIs治疗结果相关，在PT阈值上p < 0.05。在PGRN-AMPS样本中，尽责性的PGS与SSRIs治疗反应之间也发现了显著的关联。在跨性状GWAS meta分析中，我们确定了8个位点与(a) SSRI反应和YEATS4基因附近的责任心相关，(b) SSRI缓解和神经质相关，8个位点与PRAG1、MSRA、XKR6、ELAVL2、PLXNC1、PLEKHM1和BRUNOL4基因附近的基因相关。对人格特征的多基因负荷的评估可能有助于结合临床数据来预测重度抑郁症患者是否可能对SSRIs有良好的反应。
Studies reported a strong genetic correlation between the Big Five personality traits and major depressive disorder (MDD). Moreover, personality traits are thought to be associated with response to antidepressants treatment that might partly be mediated by genetic factors. In this study, we examined whether polygenic scores (PGSs) derived from the Big Five personality traits predict treatment response and remission in patients with MDD who were prescribed selective serotonin reuptake inhibitors (SSRIs). In addition, we performed meta-analyses of genome-wide association studies (GWASs) on these traits to identify genetic variants underpinning the cross-trait polygenic association. The PGS analysis was performed using data from two cohorts: the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS, n = 529) and the International SSRI Pharmacogenomics Consortium (ISPC, n = 865). The cross-trait GWAS meta-analyses were conducted by combining GWAS summary statistics on SSRIs treatment outcome and on the personality traits. The results showed that the PGS for openness and neuroticism were associated with SSRIs treatment outcomes at p < 0.05 across PT thresholds in both cohorts. A significant association was also found between the PGS for conscientiousness and SSRIs treatment response in the PGRN-AMPS sample. In the cross-trait GWAS meta-analyses, we identified eight loci associated with (a) SSRIs response and conscientiousness near YEATS4 gene and (b) SSRI remission and neuroticism eight loci near PRAG1, MSRA, XKR6, ELAVL2, PLXNC1, PLEKHM1, and BRUNOL4 genes. An assessment of a polygenic load for personality traits may assist in conjunction with clinical data to predict whether MDD patients might respond favorably to SSRIs.
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影响因子：
7.4
作者：
Baune, Bernhard T.;Hohoff, Christa;Domschke, Katharina
通讯作者：
Domschke, Katharina
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
3.1
作者：
Andrade, L;Caraveo-Anduaga, JJ;Wittchen, HU
通讯作者：
Wittchen, HU
影响因子：
11
作者：
通讯作者：
--
影响因子：
7.6
作者：
Baune, Bernhard T.;Hohoff, Christa;Domschke, Katharina
通讯作者：
Domschke, Katharina