Frontiers in Psychiatry (Mar 2018)
Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder
- Azmeraw T. Amare,
- Klaus Oliver Schubert,
- Klaus Oliver Schubert,
- Fasil Tekola-Ayele,
- Yi-Hsiang Hsu,
- Yi-Hsiang Hsu,
- 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,
- Chen-Jee Hong,
- Ari Illi,
- Yuan Ji,
- Olli Kampman,
- Olli Kampman,
- Toshihiko Kinoshita,
- Esa Leinonen,
- Esa Leinonen,
- Ying-Jay Liou,
- 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,
- Shih-Jen Tsai,
- Michiaki Kubo,
- Teri E. Klein,
- Richard M. Weinshilboum,
- Joanna M. Biernacka,
- Joanna M. Biernacka,
- Bernhard T. Baune
Affiliations
- Azmeraw T. Amare
- Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia
- Klaus Oliver Schubert
- Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia
- Klaus Oliver Schubert
- Northern Adelaide Local Health Network, Mental Health Services, Adelaide, SA, Australia
- Fasil Tekola-Ayele
- Epidemiology Branch, Division of Intramural Population Health Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
- Yi-Hsiang Hsu
- HSL Institute for Aging Research, Harvard Medical School, Boston, MA, United States
- Yi-Hsiang Hsu
- Program for Quantitative Genomics, Harvard School of Public Health, Boston, MA, United States
- Yi-Hsiang Hsu
- Broad Institute of MIT and Harvard, Cambridge, MA, United States
- Katrin Sangkuhl
- Biomedical Data Science, Stanford University, Stanford, CA, United States
- Gregory Jenkins
- Department of Health Sciences Research, Mayo Clinic, Rochester, NY, United States
- Ryan M. Whaley
- Biomedical Data Science, Stanford University, Stanford, CA, United States
- Poulami Barman
- Department of Health Sciences Research, Mayo Clinic, Rochester, NY, United States
- Anthony Batzler
- Department of Health Sciences Research, Mayo Clinic, Rochester, NY, United States
- Russ B. Altman
- Department of Bioengineering, Stanford University, Stanford, CA, United States
- Volker Arolt
- 0Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany
- Jürgen Brockmöller
- 1Department of Clinical Pharmacology, University Göttingen, Göttingen, Germany
- Chia-Hui Chen
- 2Department of Psychiatry, Taipei Medical University-Shuangho Hospital, New Taipei City, Taiwan
- Katharina Domschke
- 3Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Daniel K. Hall-Flavin
- 4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, NY, United States
- Chen-Jee Hong
- 5Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
- Chen-Jee Hong
- 6Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Ari Illi
- 7Department of Psychiatry, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Yuan Ji
- 8Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Rochester, Rochester, MN, United States
- Olli Kampman
- 7Department of Psychiatry, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Olli Kampman
- 9Department of Psychiatry, Seinäjoki Hospital District, Seinäjoki, Finland
- Toshihiko Kinoshita
- 0Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan
- Esa Leinonen
- 7Department of Psychiatry, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Esa Leinonen
- 1Department of Psychiatry, Tampere University Hospital, Tampere, Finland
- Ying-Jay Liou
- 5Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
- Ying-Jay Liou
- 6Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Taisei Mushiroda
- 2RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan
- Shinpei Nonen
- 3Department of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan
- Michelle K. Skime
- 4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, NY, United States
- Liewei Wang
- 8Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Rochester, Rochester, MN, United States
- Masaki Kato
- 0Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan
- Yu-Li Liu
- 4Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan
- Verayuth Praphanphoj
- 5Center for Medical Genetics Research, Rajanukul Institute, Department of Mental Health, Ministry of Public Health Bangkok, Bangkok, Thailand
- Julia C. Stingl
- 6Research Division Federal Institute for Drugs and Medical Devices, Bonn, Germany
- William V. Bobo
- 4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, NY, United States
- Shih-Jen Tsai
- 5Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
- Shih-Jen Tsai
- 6Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Michiaki Kubo
- 2RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan
- Teri E. Klein
- Biomedical Data Science, Stanford University, Stanford, CA, United States
- Richard M. Weinshilboum
- 8Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Rochester, Rochester, MN, United States
- Joanna M. Biernacka
- Department of Health Sciences Research, Mayo Clinic, Rochester, NY, United States
- Joanna M. Biernacka
- 4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, NY, United States
- Bernhard T. Baune
- Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia
- DOI
- https://doi.org/10.3389/fpsyt.2018.00065
- Journal volume & issue
-
Vol. 9
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
- pharmacogenomics
- polygenic score
- personality traits
- major depression
- antidepressants
- selective serotonin reuptake inhibitors
