title: Polygenic risk scores in bipolar disorder subgroups.
abstract: BACKGROUND
  Bipolar disorder (BD) is a genetically and clinically heterogeneous disorder. Current classifications of BD rely on clinical presentations without any validating biomarkers, making homogenous and valid subtypes warranted. This study aims at investigating whether a BD polygenic risk score (PGRS) can validate BD subtypes including diagnostic sub-categories (BD-I versus BD-II), patients with and without psychotic symptoms, polarity of first presenting episode and age at onset based groups. We also wanted to investigate whether illness severity indicators were associated with a higher polygenic risk for BD.
  
  
  METHODS
  Analyze differences in BD PGRS scores between suggested subtypes of BD and between healthy controls (CTR) and BD in a sample of N=669 (255 BD and 414 CTR).
  
  
  RESULTS
  The BD PGRS significantly discriminates between BD and CTR (p<0.001). There were no differences in BD PGRS between groups defined by diagnostic sub-categories, presenting polarity and age at onset. Patients with psychotic BD had nominally significantly higher BD PGRS than patients with non-psychotic BD after controlling for diagnostic sub-category (p=0.019). These findings remained trend level significant after Bonferroni corrections (p=0.079).
  
  
  CONCLUSIONS
  The low explained variance of the current PGRS method could lead to type II errors.
  
  
  CONCLUSIONS
  There are nominally significant differences in BD PGRS scores between patients with and without psychotic symptoms, indicating that these two forms of BD might represent distinct subtypes of BD based in its polygenic architecture and a division between BD with and without psychotic symptoms could represent a more valid subclassification of BD than current diagnostic sub-categories. If replicated, this finding could affect future research, diagnostics and clinical practice.
authors.affiliation: Department of Specialized Inpatient Treatment, Division of Mental Health Services, Akershus University Hospital, Norway; NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: s.r.aminoff@medisin.uio.no.
authors.forename: Sofie Ragnhild
authors.initials: SR
authors.lastname: Aminoff
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Martin
authors.initials: M
authors.lastname: Tesli
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bettella
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Monica
authors.initials: M
authors.lastname: Aas
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Trine Vik
authors.initials: TV
authors.lastname: Lagerberg
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D011618:Psychotic Disorders / Q000145:classification / Q000175:diagnosis; D012306:Risk
keywords: Bipolar disorder; Depression; Hypomania; Mania; Polygenic risk score; Psychosis