title: Bipolar disorder and its relation to major psychiatric disorders: a family-based study in the Swedish population.
abstract: OBJECTIVE
  Bipolar disorder (BPD) shares genetic components with other psychiatric disorders; however, uncertainty remains about where in the psychiatric spectra BPD falls. To understand the etiology of BPD, we studied the familial aggregation of BPD and co-aggregation between BPD and schizophrenia, depression, anxiety disorders, attention-deficit hyperactivity disorder, drug abuse, personality disorders, and autism spectrum disorders.
  
  
  METHODS
  A population-based cohort was created by linking several Swedish national registers. A total of 54,723 individuals with BPD were identified among 8,141,033 offspring from 4,149,748 nuclear families. The relative risk of BPD in relatives and the co-occurrence of other psychiatric disorders in patients with BPD and their relatives were compared to those of matched-population controls. Structural equation modeling was used to estimate the heritability and tetrachoric correlation.
  
  
  RESULTS
  The familial risks for relatives of BPD probands were 5.8-7.9 in first-degree relatives, and decreased with genetic distance. Co-occurrence risks for other psychiatric disorders were 9.7-22.9 in individuals with BPD and 1.7-2.8 in full siblings of BPD probands. Heritability for BPD was estimated at 58%. The correlations between BPD and other psychiatric disorders were considerable (0.37-0.62) and primarily due to genetic effects. The correlation with depression was the highest (0.62), and was 0.44 for schizophrenia.
  
  
  CONCLUSIONS
  The high familial risks provide evidence that genetic factors play an important role in the etiology of BPD, and the shared genetic determinants suggest pleiotropic effects across different psychiatric disorders. Results also indicate that BPD is in both the mood and psychotic spectra, but possibly more closely related to mood disorders.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Bergen
authors.forename: Ralf
authors.initials: R
authors.lastname: Kuja-Halkola
authors.forename: Henrik
authors.initials: H
authors.lastname: Larsson
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000453:epidemiology / Q000235:genetics*; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics*; D000067877:Autism Spectrum Disorder / Q000453:epidemiology / Q000235:genetics; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D003866:Depressive Disorder / Q000453:epidemiology / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D010554:Personality Disorders / Q000453:epidemiology / Q000235:genetics; D012042:Registries; D012306:Risk; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D035781:Siblings; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics; D013548:Sweden / Q000453:epidemiology; D014427:Twins / Q000235:genetics
keywords: genetic epidemiology; heritability; relative risk