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, 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 KinoshitaEsa Leinonen, Ying Jay Liou, Taisei Mushiroda, Shinpei Nonen, Michelle K. Skime, Liewei M 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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article number65
JournalFrontiers in Psychiatry
Volume9
Issue numberMAR
DOIs
StatePublished - Mar 6 2018

Fingerprint

Major Depressive Disorder
Serotonin Uptake Inhibitors
Personality
Genome-Wide Association Study
Meta-Analysis
Pharmacogenetics
Antidepressive Agents
Multifactorial Inheritance
Genes
Therapeutics
Research

Keywords

  • Antidepressants
  • Major depression
  • Personality traits
  • Pharmacogenomics
  • Polygenic score
  • Selective serotonin reuptake inhibitors

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Association of the polygenic scores for personality traits and response to selective serotonin reuptake inhibitors in patients with major depressive disorder. / Amare, Azmeraw T.; Schubert, Klaus Oliver; Tekola-Ayele, Fasil; Hsu, Yi Hsiang; Sangkuhl, Katrin; Jenkins, Gregory; Whaley, Ryan M.; Barman, Poulami; Batzler, Anthony; Altman, Russ B.; Arolt, Volker; Brockmöller, Jürgen; Chen, Chia Hui; Domschke, Katharina; Hall-Flavin, Daniel K.; Hong, Chen Jee; Illi, Ari; Ji, Yuan; Kampman, Olli; Kinoshita, Toshihiko; Leinonen, Esa; Liou, Ying Jay; Mushiroda, Taisei; Nonen, Shinpei; Skime, Michelle K.; Wang, Liewei M; Kato, Masaki; Liu, Yu Li; Praphanphoj, Verayuth; Stingl, Julia C.; Bobo, William V; Tsai, Shih Jen; Kubo, Michiaki; Klein, Teri E.; Weinshilboum, Richard M; Biernacka, Joanna M; Baune, Bernhard T.

In: Frontiers in Psychiatry, Vol. 9, No. MAR, 65, 06.03.2018.

Research output: Contribution to journalArticle

Amare, AT, Schubert, KO, Tekola-Ayele, F, Hsu, YH, Sangkuhl, K, Jenkins, G, Whaley, RM, Barman, P, Batzler, A, Altman, RB, Arolt, V, Brockmöller, J, Chen, CH, Domschke, K, Hall-Flavin, DK, Hong, CJ, Illi, A, Ji, Y, Kampman, O, Kinoshita, T, Leinonen, E, Liou, YJ, Mushiroda, T, Nonen, S, Skime, MK, Wang, LM, Kato, M, Liu, YL, Praphanphoj, V, Stingl, JC, Bobo, WV, Tsai, SJ, Kubo, M, Klein, TE, Weinshilboum, RM, Biernacka, JM & Baune, BT 2018, 'Association of the polygenic scores for personality traits and response to selective serotonin reuptake inhibitors in patients with major depressive disorder', Frontiers in Psychiatry, vol. 9, no. MAR, 65. https://doi.org/10.3389/fpsyt.2018.00065
Amare, Azmeraw T. ; Schubert, Klaus Oliver ; Tekola-Ayele, Fasil ; Hsu, Yi Hsiang ; Sangkuhl, Katrin ; Jenkins, Gregory ; Whaley, Ryan M. ; Barman, Poulami ; Batzler, Anthony ; Altman, Russ B. ; Arolt, Volker ; Brockmöller, Jürgen ; Chen, Chia Hui ; Domschke, Katharina ; Hall-Flavin, Daniel K. ; Hong, Chen Jee ; Illi, Ari ; Ji, Yuan ; Kampman, Olli ; Kinoshita, Toshihiko ; Leinonen, Esa ; Liou, Ying Jay ; Mushiroda, Taisei ; Nonen, Shinpei ; Skime, Michelle K. ; Wang, Liewei M ; Kato, Masaki ; Liu, Yu Li ; Praphanphoj, Verayuth ; Stingl, Julia C. ; Bobo, William V ; Tsai, Shih Jen ; Kubo, Michiaki ; Klein, Teri E. ; Weinshilboum, Richard M ; Biernacka, Joanna M ; Baune, Bernhard T. / Association of the polygenic scores for personality traits and response to selective serotonin reuptake inhibitors in patients with major depressive disorder. In: Frontiers in Psychiatry. 2018 ; Vol. 9, No. MAR.
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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.",
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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 M

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.

PY - 2018/3/6

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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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