The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression

被引：22

作者：

Amare, Azmeraw T. ^{[1
,2
]}

Schubert, Klaus Oliver ^{[1
,3
]}

Tekola-Ayele, Fasil ^{[4
]}

Hsu, Yi-Hsiang ^{[5
,6
]}

Sangkuhl, Katrin ^{[7
]}

Jenkins, Gregory ^{[8
]}

Whaley, Ryan M. ^{[7
]}

Barman, Poulami ^{[8
]}

Batzler, Anthony ^{[8
]}

Altman, Russ B. ^{[9
]}

Arolt, Volker ^{[10
]}

Brockmoeller, Juergen ^{[11
]}

Chen, Chia-Hui ^{[12
]}

Domschke, Katharina ^{[13
]}

Hall-Flavin, Daniel K. ^{[14
]}

Hong, Chen-Jee ^{[15
,16
]}

Illi, Ari ^{[17
]}

Ji, Yuan ^{[18
]}

Kampman, Olli ^{[17
,19
]}

Kinoshita, Toshihiko ^{[20
]}

Leinonen, Esa ^{[17
,21
]}

Liou, Ying-Jay ^{[15
,16
]}

Mushiroda, Taisei ^{[22
]}

Nonen, Shinpei ^{[23
]}

Skime, Michelle K. ^{[14
]}

Wang, Liewei ^{[18
]}

Kato, Masaki ^{[20
]}

Liu, Yu-Li ^{[24
]}

Praphanphoj, Verayuth ^{[25
]}

Stingl, Julia C. ^{[26
]}

Bobo, William V. ^{[14
]}

Tsai, Shih-Jen ^{[15
,16
]}

Kubo, Michiaki ^{[22
]}

Klein, Teri E. ^{[7
]}

Weinshilboum, Richard M. ^{[18
]}

Biernacka, Joanna M. ^{[8
,14
]}

Baune, Bernhard T. ^{[1
]}

机构：

[1] Univ Adelaide, Sch Med, Discipline Psychiat, North Terrace, Adelaide, SA 5005, Australia

[2] SAHMRI, South Australian Acad Hlth Sci & Translat Ctr, Adelaide, SA, Australia

[3] Northern Adelaide Local Hlth Network, Mental Hlth Serv, Adelaide, SA, Australia

[4] NICHHD, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA

[5] Harvard Med Sch, HSL Inst Aging Res, Boston, MA USA

[6] Harvard Sch Publ Hlth, Program Quantitat Genom, Boston, MA USA

[7] Stanford Univ, Biomed Data Sci, Stanford, CA 94305 USA

[8] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[9] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[10] Univ Munster, Dept Psychiat & Psychotherapy, Munster, Germany

[11] Univ Gottingen, Dept Clin Pharmacol, Gottingen, Germany

[12] Taipei Med Univ, Shuangho Hosp, Dept Psychiat, New Taipei, Taiwan

[13] Univ Freiburg, Dept Psychiat & Psychotherapy, Fac Med, Freiburg, Germany

[14] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA

[15] Taipei Vet Gen Hosp, Dept Psychiat, Taipei, Taiwan

[16] Natl Yang Ming Univ, Sch Med, Div Psychiat, Taipei, Taiwan

[17] Univ Tampere, Fac Med & Life Sci, Dept Psychiat, Tampere, Finland

[18] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA

[19] Seinajoki Hosp Dist, Dept Psychiat, Seinajoki, Finland

[20] Kansai Med Univ, Dept Neuropsychiat, Osaka, Japan

[21] Tampere Univ Hosp, Dept Psychiat, Tampere, Finland

[22] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[23] Hyogo Univ Hlth Sci, Dept Pharm, Kobe, Hyogo, Japan

[24] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Miaoli, Taiwan

[25] Minist Publ Hlth Bangkok, Rajanukul Inst, Dept Mental Hlth, Med Genet Res Ctr, Bangkok, Thailand

[26] Fed Inst Drugs & Med Devices, Div Res, Bonn, Germany

来源：

JOURNAL OF NEURAL TRANSMISSION | 2019年 / 126卷 / 01期

关键词：

Pharmacogenomics; Polygenic score; Major depression; Antidepressants; SSRIs; Obesity; Body mass index; Coronary artery disease; Pleiotropy; SEQUENCED TREATMENT ALTERNATIVES; MEDICAL COMORBIDITY; HEART-DISEASE; DISORDER; PROTEIN; ANTIDEPRESSANTS; POPULATION; EXPRESSION; RATIONALE; NEGR1;

D O I：

10.1007/s00702-018-01966-x

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants for the treatment of major depressive disorder (MDD). However, treatment response during an initial therapeutic trial is often poor and is difficult to predict. Heterogeneity of response to SSRIs in depressed patients is partly driven by co-occurring somatic disorders such as coronary artery disease (CAD) and obesity. CAD and obesity may also be associated with metabolic side effects of SSRIs. In this study, we assessed the association of CAD and obesity with treatment response to SSRIs in patients with MDD using a polygenic score (PGS) approach. Additionally, we performed cross-trait meta-analyses to pinpoint genetic variants underpinnings the relationship of CAD and obesity with SSRIs treatment response. First, PGSs were calculated at different p value thresholds (P-T) for obesity and CAD. Next, binary logistic regression was applied to evaluate the association of the PGSs to SSRIs treatment response in a discovery sample (ISPC, N=865), and in a replication cohort (STAR*D, N=1,878). Finally, a cross-trait GWAS meta-analysis was performed by combining summary statistics. We show that the PGSs for CAD and obesity were inversely associated with SSRIs treatment response. At the most significant thresholds, the PGS for CAD and body mass index accounted 1.3%, and 0.8% of the observed variability in treatment response to SSRIs, respectively. In the cross-trait meta-analyses, we identified (1) 14 genetic loci (including NEGR1, CADM2, PMAIP1, PARK2) that are associated with both obesity and SSRIs treatment response; (2) five genetic loci (LINC01412, PHACTR1, CDKN2B, ATXN2, KCNE2) with effects on CAD and SSRIs treatment response. Our findings implicate that the genetic variants of CAD and obesity are linked to SSRIs treatment response in MDD. A better SSRIs treatment response might be achieved through a stratified allocation of treatment for MDD patients with a genetic risk for obesity or CAD.

引用

页码：35 / 45

页数：11

共 50 条

[1] The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression
Azmeraw T. Amare
Klaus Oliver Schubert
Fasil Tekola-Ayele
Yi-Hsiang Hsu
Katrin Sangkuhl
Gregory Jenkins
Ryan M. Whaley
Poulami Barman
Anthony Batzler
Russ B. Altman
Volker Arolt
Jürgen Brockmöller
Chia-Hui Chen
Katharina Domschke
Daniel K. Hall-Flavin
Chen-Jee Hong
Ari Illi
Yuan Ji
Olli Kampman
Toshihiko Kinoshita
Esa Leinonen
Ying-Jay Liou
Taisei Mushiroda
Shinpei Nonen
Michelle K. Skime
Liewei Wang
Masaki Kato
Yu-Li Liu
Verayuth Praphanphoj
Julia C. Stingl
William V. Bobo
Shih-Jen Tsai
Michiaki Kubo
Teri E. Klein
Richard M. Weinshilboum
Joanna M. Biernacka
Bernhard T. Baune
[J]. Journal of Neural Transmission, 2019, 126 : 35 - 45
[2] Major Depression and Coronary Artery Disease
Vieweg, W. Victor R.
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[3] HPA axis genes and clinical outcome and response to SSRIs in major depression
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