Association of schizophrenia polygenic risk score with manic and depressive psychosis in bipolar disorder

Matej Markota, Brandon J. Coombes, Beth R. Larrabee, Susan L. McElroy, David J. Bond, Marin D Veldic, Colin L. Colby, Mohit Chauhan, Alfredo B. Cuellar-Barboza, Manuel Fuentes, Simon Kung, Miguel L. Prieto, Teresa A. Rummans, William V Bobo, Mark A Frye, Joanna M Biernacka

Research output: Contribution to journalArticle

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Abstract

Bipolar disorder (BD) is highly heterogeneous in symptomatology. Narrowing the clinical phenotype may increase the power to identify risk genes that contribute to particular BD subtypes. This study was designed to test the hypothesis that genetic overlap between schizophrenia (SZ) and BD is higher for BD with a history of manic psychosis. Analyses were conducted using a Mayo Clinic Bipolar Biobank cohort of 957 bipolar cases (including 333 with history of psychosis during mania, 64 with history of psychosis only during depression, 547 with no history of psychosis, and 13 with unknown history of psychosis) and 778 controls. Polygenic risk score (PRS) analysis was performed by calculating a SZ-PRS for the BD cases and controls, and comparing the calculated SZ risk between different psychosis subgroups and bipolar types. The SZ-PRS was significantly higher for BD-I cases with manic psychosis than BD-I cases with depressive psychosis (Nagelkerke’s R2 = 0.021; p = 0.045), BD-I cases without psychosis (R2 = 0.015; p = 0.007), BD-II cases without psychosis (R2 = 0.014; p = 0.017), and controls (R2 = 0.065; p = 2 × 10−13). No other significant differences were found. Our results show that BD-I with manic psychosis is genetically more similar to SZ than any other tested BD subgroup. Further investigations on genetics of distinct clinical phenotypes composing major psychoses may help refine the current diagnostic classification system.

Original languageEnglish (US)
Article number188
JournalTranslational Psychiatry
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Bipolar Disorder
Psychotic Disorders
Schizophrenia
Phenotype
Depression

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Association of schizophrenia polygenic risk score with manic and depressive psychosis in bipolar disorder. / Markota, Matej; Coombes, Brandon J.; Larrabee, Beth R.; McElroy, Susan L.; Bond, David J.; Veldic, Marin D; Colby, Colin L.; Chauhan, Mohit; Cuellar-Barboza, Alfredo B.; Fuentes, Manuel; Kung, Simon; Prieto, Miguel L.; Rummans, Teresa A.; Bobo, William V; Frye, Mark A; Biernacka, Joanna M.

In: Translational Psychiatry, Vol. 8, No. 1, 188, 01.12.2018.

Research output: Contribution to journalArticle

Markota, M, Coombes, BJ, Larrabee, BR, McElroy, SL, Bond, DJ, Veldic, MD, Colby, CL, Chauhan, M, Cuellar-Barboza, AB, Fuentes, M, Kung, S, Prieto, ML, Rummans, TA, Bobo, WV, Frye, MA & Biernacka, JM 2018, 'Association of schizophrenia polygenic risk score with manic and depressive psychosis in bipolar disorder', Translational Psychiatry, vol. 8, no. 1, 188. https://doi.org/10.1038/s41398-018-0242-3
Markota, Matej ; Coombes, Brandon J. ; Larrabee, Beth R. ; McElroy, Susan L. ; Bond, David J. ; Veldic, Marin D ; Colby, Colin L. ; Chauhan, Mohit ; Cuellar-Barboza, Alfredo B. ; Fuentes, Manuel ; Kung, Simon ; Prieto, Miguel L. ; Rummans, Teresa A. ; Bobo, William V ; Frye, Mark A ; Biernacka, Joanna M. / Association of schizophrenia polygenic risk score with manic and depressive psychosis in bipolar disorder. In: Translational Psychiatry. 2018 ; Vol. 8, No. 1.
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AU - Colby, Colin L.

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AU - Prieto, Miguel L.

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