title: Polygenic dissection of the bipolar phenotype.
abstract: BACKGROUND
  Recent data provide strong support for a substantial common polygenic  contribution (i.e. many alleles each of small effect) to genetic  susceptibility for schizophrenia and overlapping susceptibility for bipolar  disorder.
  
  
  OBJECTIVE
  To test hypotheses about the relationship between schizophrenia and  psychotic types of bipolar disorder.
  
  
  METHODS
  Using a polygenic score analysis to test whether schizophrenia polygenic  risk alleles, en masse, significantly discriminate between individuals with  bipolar disorder with and without psychotic features. The primary sample  included 1829 participants with bipolar disorder and the replication sample  comprised 506 people with bipolar disorder.
  
  
  RESULTS
  The subset of participants with Research Diagnostic Criteria  schizoaffective bipolar disorder (n = 277) were significantly  discriminated from the remaining participants with bipolar disorder  (n = 1552) in both the primary (P = 0.00059) and the  replication data-sets (P = 0.0070). In contrast, those with psychotic  bipolar disorder as a whole were not significantly different from those with  non-psychotic bipolar disorder in either data-set.
  
  
  CONCLUSIONS
  Genetic susceptibility influences at least two major domains of  psychopathological variation in the schizophrenia-bipolar disorder  clinical spectrum: one that relates to expression of a 'bipolar  disorder-like' phenotype and one that is associated with expression of  'schizophrenia-like' psychotic symptoms.
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK.
authors.forename: M L
authors.initials: ML
authors.lastname: Hamshere
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: I R
authors.initials: IR
authors.lastname: Jones
authors.forename: L
authors.initials: L
authors.lastname: Jones
authors.forename: G
authors.initials: G
authors.lastname: Kirov
authors.forename: E K
authors.initials: EK
authors.lastname: Green
authors.forename: V
authors.initials: V
authors.lastname: Moskvina
authors.forename: D
authors.initials: D
authors.lastname: Grozeva
authors.forename: N
authors.initials: N
authors.lastname: Bass
authors.forename: A
authors.initials: A
authors.lastname: McQuillin
authors.forename: H
authors.initials: H
authors.lastname: Gurling
authors.forename: D
authors.initials: D
authors.lastname: St Clair
authors.forename: A H
authors.initials: AH
authors.lastname: Young
authors.forename: I N
authors.initials: IN
authors.lastname: Ferrier
authors.forename: A
authors.initials: A
authors.lastname: Farmer
authors.forename: P
authors.initials: P
authors.lastname: McGuffin
authors.forename: P
authors.initials: P
authors.lastname: Sklar
authors.forename: S
authors.initials: S
authors.lastname: Purcell
authors.forename: P A
authors.initials: PA
authors.lastname: Holmans
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: N
authors.initials: N
authors.lastname: Craddock
mesh_terms: D000293:Adolescent; D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D038801:International Classification of Diseases; D016015:Logistic Models; D020412:Multifactorial Inheritance; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D006113:United Kingdom