New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation

被引：35

作者：

Fabbri, C. ^{[1
,2
]}

Tansey, K. E. ^{[3
]}

Perlis, R. H. ^{[4
]}

Hauser, J. ^{[5
]}

Henigsberg, N. ^{[6
]}

Maier, W. ^{[7
]}

Mors, O. ^{[8
]}

Placentino, A. ^{[9
,10
]}

Rietschel, M. ^{[11
]}

Souery, D. ^{[12
,13
]}

Breen, G. ^{[2
]}

Curtis, C. ^{[2
]}

Sang-Hyuk, L. ^{[2
]}

Newhouse, S. ^{[2
]}

Patel, H. ^{[2
]}

Guipponi, M. ^{[14
,15
]}

Perroud, N. ^{[16
]}

Bondolfi, G. ^{[16
]}

O'Donovan, M. ^{[17
]}

Lewis, G. ^{[18
]}

Biernacka, J. M. ^{[19
,20
]}

Weinshilboum, R. M. ^{[21
]}

Farmer, A. ^{[1
]}

Aitchison, K. J. ^{[22
]}

Craig, I ^{[2
]}

McGuffin, P. ^{[2
]}

Uher, R. ^{[23
]}

Lewis, C. M. ^{[2
]}

机构：

[1] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy

[2] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England

[3] Cardiff Univ, Coll Biomed & Life Sci, Cardiff, S Glam, Wales

[4] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA

[5] Poznan Univ Med Sci, Dept Psychiat, Lab Psychiat Genet, Poznan, Poland

[6] Univ Zagreb, Med Sch, Croatian Inst Brain Res, Zagreb, Croatia

[7] Univ Bonn, Dept Psychiat, Bonn, Germany

[8] Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark

[9] Fatebenefratelli, Biol Psychiat Unit, Ctr San Giovanni di Dio, Ist Ricovero & Cura Carattere Sci, Brescia, Italy

[10] Fatebenefratelli, Dual Diag Ward, Ctr San Giovanni di Dio, Ist Ricovero & Cura Carattere Sci, Brescia, Italy

[11] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, Mannheim, Germany

[12] Univ Libre Bruxelles, Lab Psychol Med, Brussels, Belgium

[13] Psy Pluriel Ctr Europeen Psychol Med, Brussels, Belgium

[14] Univ Geneva, Dept Genet Med & Dev, Med Sch, Geneva, Switzerland

[15] Univ Hosp Geneva, Geneva, Switzerland

[16] Univ Geneva, Dept Psychiat, Geneva, Switzerland

[17] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Sch Med, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales

[18] UCL, Div Psychiat, London, England

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

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

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

[22] Univ Alberta, Dept Psychiat, Edmonton, AB, Canada

[23] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada

来源：

PHARMACOGENOMICS JOURNAL | 2018年 / 18卷 / 03期

基金：

英国医学研究理事会;

关键词：

MAJOR DEPRESSIVE DISORDER; GENOME-WIDE ASSOCIATION; DOUBLE-BLIND; NEURONAL DIFFERENTIATION; GENETIC-VARIANTS; MOOD DISORDERS; LARGE-SCALE; POPULATION; PROTEIN; SCHIZOPHRENIA;

D O I：

10.1038/tpj.2017.44

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (5NP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMED5 consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P= 1.80e - 08, ITGA9 (integrin a9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO:0044427 (chromosomal part) were associated with improvement (corrected P=0,007 and 0,045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophns and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying their role.

引用

页码：413 / 421

页数：9

共 78 条

[1] Full UPF3B function is critical for neuronal differentiation of neural stem cells [J].

Alrahbeni, Tahani ;

Sartor, Francesca ;

Anderson, Jihan ;

Miedzybrodzka, Zosia ;

McCaig, Colin ;

Mueller, Berndt .

MOLECULAR BRAIN, 2015, 8

[2] The glucocorticoid receptor: Pivot of depression and of antidepressant treatment? [J].

Anacker, Christoph ;

Zunszain, Patricia A. ;

Carvalho, Livia A. ;

Pariante, Carmine M. .

PSYCHONEUROENDOCRINOLOGY, 2011, 36 (03) :415-425

[3] Data quality control in genetic case-control association studies [J].

Anderson, Carl A. ;

Pettersson, Fredrik H. ;

Clarke, Geraldine M. ;

Cardon, Lon R. ;

Morris, Andrew P. ;

Zondervan, Krina T. .

NATURE PROTOCOLS, 2010, 5 (09) :1564-1573

[4]

[Anonymous], 2013, AM J PSYCHIAT, V170, P207, DOI DOI 10.1176/appi.ajp.2012.12020237

[5] DISC1-TSNAX and DAOA genes in major depression and citalopram efficacy [J].

Arias, Barbara ;

Fabbri, Chiara ;

Serretti, Alessandro ;

Drago, Antonio ;

Mitjans, Marina ;

Gasto, Cristobal ;

Catalan, Rosa ;

Fananas, Lourdes .

JOURNAL OF AFFECTIVE DISORDERS, 2014, 168 :91-97

[6] AN INVENTORY FOR MEASURING DEPRESSION [J].

BECK, AT ;

ERBAUGH, J ;

WARD, CH ;

MOCK, J ;

MENDELSOHN, M .

ARCHIVES OF GENERAL PSYCHIATRY, 1961, 4 (06) :561-&

[7] Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode [J].

Belzeaux, R. ;

Bergon, A. ;

Jeanjean, V. ;

Loriod, B. ;

Formisano-Treziny, C. ;

Verrier, L. ;

Loundou, A. ;

Baumstarck-Barrau, K. ;

Boyer, L. ;

Gall, V. ;

Gabert, J. ;

Nguyen, C. ;

Azorin, J-M ;

Naudin, J. ;

Ibrahim, E. C. .

TRANSLATIONAL PSYCHIATRY, 2012, 2 :e185-e185

[8] The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response [J].

Biernacka, J. M. ;

Sangkuhl, K. ;

Jenkins, G. ;

Whaley, R. M. ;

Barman, P. ;

Batzler, A. ;

Altman, R. B. ;

Arolt, V. ;

Brockmoeller, J. ;

Chen, C. H. ;

Domschke, K. ;

Hall-Flavin, D. K. ;

Hong, C. J. ;

Illi, A. ;

Ji, Y. ;

Kampman, O. ;

Kinoshita, T. ;

Leinonen, E. ;

Liou, Y. J. ;

Mushiroda, T. ;

Nonen, S. ;

Skime, M. K. ;

Wang, L. ;

Baune, B. T. ;

Kato, M. ;

Liu, Y. L. ;

Praphanphoj, V. ;

Stingl, J. C. ;

Tsai, S. J. ;

Kubo, M. ;

Klein, T. E. ;

Weinshilboum, R. .

TRANSLATIONAL PSYCHIATRY, 2015, 5 :e553-e553

[9]

Bondolfi G, 2006, SWISS MED WKLY, V136, P78

[10] Processing of the Synaptic Cell Adhesion Molecule Neurexin-3β by Alzheimer Disease α- and γ-Secretases [J].

Bot, Nathalie ;

Schweizer, Claude ;

Ben Halima, Saoussen ;

Fraering, Patrick C. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (04) :2762-2773

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