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Front Psychiatry. 2018 Mar 6;9:65. doi: 10.3389/fpsyt.2018.00065. eCollection 2018.

Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder.

Author information

1
Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
2
Northern Adelaide Local Health Network, Mental Health Services, Adelaide, SA, Australia.
3
Epidemiology Branch, Division of Intramural Population Health Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
4
HSL Institute for Aging Research, Harvard Medical School, Boston, MA, United States.
5
Program for Quantitative Genomics, Harvard School of Public Health, Boston, MA, United States.
6
Broad Institute of MIT and Harvard, Cambridge, MA, United States.
7
Biomedical Data Science, Stanford University, Stanford, CA, United States.
8
Department of Health Sciences Research, Mayo Clinic, Rochester, NY, United States.
9
Department of Bioengineering, Stanford University, Stanford, CA, United States.
10
Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
11
Department of Clinical Pharmacology, University Göttingen, Göttingen, Germany.
12
Department of Psychiatry, Taipei Medical University-Shuangho Hospital, New Taipei City, Taiwan.
13
Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
14
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, NY, United States.
15
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
16
Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
17
Department of Psychiatry, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
18
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Rochester, Rochester, MN, United States.
19
Department of Psychiatry, Seinäjoki Hospital District, Seinäjoki, Finland.
20
Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
21
Department of Psychiatry, Tampere University Hospital, Tampere, Finland.
22
RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
23
Department of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan.
24
Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
25
Center for Medical Genetics Research, Rajanukul Institute, Department of Mental Health, Ministry of Public Health Bangkok, Bangkok, Thailand.
26
Research Division Federal Institute for Drugs and Medical Devices, Bonn, Germany.

Abstract

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.

KEYWORDS:

antidepressants; major depression; personality traits; pharmacogenomics; polygenic score; selective serotonin reuptake inhibitors

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