TY - JOUR
T1 - Association of the polygenic scores for personality traits and response to selective serotonin reuptake inhibitors in patients with major depressive disorder
AU - Amare, Azmeraw T.
AU - Schubert, Klaus Oliver
AU - Tekola-Ayele, Fasil
AU - Hsu, Yi Hsiang
AU - Sangkuhl, Katrin
AU - Jenkins, Gregory
AU - Whaley, Ryan M.
AU - Barman, Poulami
AU - Batzler, Anthony
AU - Altman, Russ B.
AU - Arolt, Volker
AU - Brockmöller, Jürgen
AU - Chen, Chia Hui
AU - Domschke, Katharina
AU - Hall-Flavin, Daniel K.
AU - Hong, Chen Jee
AU - Illi, Ari
AU - Ji, Yuan
AU - Kampman, Olli
AU - Kinoshita, Toshihiko
AU - Leinonen, Esa
AU - Liou, Ying Jay
AU - Mushiroda, Taisei
AU - Nonen, Shinpei
AU - Skime, Michelle K.
AU - Wang, Liewei
AU - Kato, Masaki
AU - Liu, Yu Li
AU - Praphanphoj, Verayuth
AU - Stingl, Julia C.
AU - Bobo, William V.
AU - Tsai, Shih Jen
AU - Kubo, Michiaki
AU - Klein, Teri E.
AU - Weinshilboum, Richard M.
AU - Biernacka, Joanna M.
AU - Baune, Bernhard T.
N1 - Funding Information:
The authors are grateful to the study subjects who participated in the studies, and we appreciate the contributions of research staffs who helped in the patient recruitment and data collection for the studies. The authors also would like to thank the National Institutes of Health (NIH), USA for making the PGRN-AMPS accessible to us. The complete clinical data for the ISPC is available at http://www.pharmgkb.org/downloads/. The PGRN-AMPS data were obtained through controlled access distributed from the NIH in the dbGaP (https://www.ncbi.nlm.nih.gov/gap). The analysis of this study was carried out using the high-performance computational capabilities of the University of Adelaide, Phoenix supercomputer (https://www.adelaide.edu.au/phoenix/). AA received a Postgraduate Research Scholarship support from the University of Adelaide through the Adelaide Scholarship International program. Funding support for the PGRN-AMPS was provided by the National Institute of General Medical Sciences, National Institutes of Health, through the PGRN grant to Principal Investigators RW and LW (U19 GM61388). Dr. D. Mrazek served as the Principal Investigator for the PGRN-AMPS study within the Mayo Clinic PGRN program. The main sources of funding for the ISPC study are presented in the earlier publication (7).
Publisher Copyright:
© 2018 Amare, Schubert, Tekola-Ayele, Hsu, Sangkuhl, Jenkins, Whaley, Barman, Batzler, Altman, Arolt, Brockmöller, Chen, Domschke, Hall-Flavin, Hong, Illi, Ji, Kampman, Kinoshita, Leinonen, Liou, Mushiroda, Nonen, Skime, Wang, Kato, Liu, Praphanphoj, Stingl, Bobo, Tsai, Kubo, Klein, Weinshilboum, Biernacka and Baune.
PY - 2018/3/6
Y1 - 2018/3/6
N2 - 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.
AB - 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.
KW - Antidepressants
KW - Major depression
KW - Personality traits
KW - Pharmacogenomics
KW - Polygenic score
KW - Selective serotonin reuptake inhibitors
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UR - http://www.scopus.com/inward/citedby.url?scp=85043306121&partnerID=8YFLogxK
U2 - 10.3389/fpsyt.2018.00065
DO - 10.3389/fpsyt.2018.00065
M3 - Article
AN - SCOPUS:85043306121
SN - 1664-0640
VL - 9
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
IS - MAR
M1 - 65
ER -