title: The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study.
abstract: OBJECTIVE
  Darier disease is an autosomal dominant skin disorder caused by mutations in the ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) gene and previously reported to cosegregate with bipolar disorder and schizophrenia in occasional pedigrees. It is, however, unknown whether these associations exist also in the general population, and the objective of this study was to examine this question.
  
  
  METHODS
  We compared a national sample of individuals with Darier disease and their first-degree relatives with matched unexposed individuals from the general population and their first-degree relatives, respectively. To examine risks for bipolar disorder and schizophrenia, risk ratios and 95% confidence intervals (CIs) were estimated using conditional logistic regressions.
  
  
  RESULTS
  Individuals with Darier disease had a 4.3 times higher risk of being diagnosed with bipolar disorder (95% CI: 2.6-7.3) and a 2.3 times higher risk of being diagnosed with schizophrenia (95% CI: 1.1-5.2) than matched individuals from the general population. Relatives of individuals with Darier disease had a 1.6 times higher risk of having bipolar disorder (95% CI: 1.1-2.5) than relatives of matched individuals from the general population, but no increased risk of schizophrenia (risk ratio = 0.8, 95% CI: 0.4-1.8).
  
  
  CONCLUSIONS
  The association between Darier disease and bipolar disorder is manifest also in the population, and our data suggest that genetic variability within the ATP2A2 gene that causes Darier disease also confers susceptibility for bipolar disorder. The Darier-causing mutations merit additional attention in molecular genetic research on bipolar disorder.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Cederlöf
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Bergen
authors.forename: Niklas
authors.initials: N
authors.lastname: Långström
authors.forename: Henrik
authors.initials: H
authors.lastname: Larsson
authors.forename: Marcus
authors.initials: M
authors.lastname: Boman
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Per
authors.initials: P
authors.lastname: Östberg
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lundström
authors.forename: Arvid
authors.initials: A
authors.lastname: Sjölander
authors.forename: Klas
authors.initials: K
authors.lastname: Nordlind
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
mesh_terms: D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D007644:Darier Disease / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016017:Odds Ratio; D010375:Pedigree; D012042:Registries; D012306:Risk; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human
keywords: Darier disease; bipolar disorder; epidemiology; schizophrenia