title: At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia.
abstract: BACKGROUND
  Schizophrenia is associated with increased risk of type II diabetes and metabolic disorders. However, it is unclear whether this comorbidity reflects shared genetic risk factors, at-risk lifestyle, or side effects of antipsychotic medication.
  
  
  METHODS
  Eleven known risk variants of type II diabetes were genotyped in patients with schizophrenia in a sample of 410 Danish patients, each matched with two healthy control subjects on sex, birth year, and month. Replication was carried out in a large multinational European sample of 4089 patients with schizophrenia and 17,597 controls (SGENE+) using Mantel-Haenszel test.
  
  
  RESULTS
  One type II diabetes at-risk allele located in TCF7L2, rs7903146 [T], was associated with schizophrenia in the discovery sample (p = .0052) and in the replication with an odds ratio of 1.07 (95% confidence interval 1.01-1.14, p = .033).
  
  
  CONCLUSIONS
  The association reported here with a well-known diabetes variant suggests that the observed comorbidity is partially caused by genetic risk variants. This study also demonstrates how genetic studies can successfully examine an epidemiologically derived hypothesis of comorbidity.
authors.affiliation: Mental Health Centre Sct. Hans, Copenhagen University Hospital, Research Institute of Biological Psychiatry, Roskilde, Denmark; Copenhagen University, Center for Pharmacogenomics, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen
authors.forename: Andrés
authors.initials: A
authors.lastname: Ingason
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.forename: Mogens
authors.initials: M
authors.lastname: Fenger
authors.forename: Omar
authors.initials: O
authors.lastname: Gustafsson
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Jakobsen
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Rasmussen
authors.forename: Sarah
authors.initials: S
authors.lastname: Tosato
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Josef
authors.initials: J
authors.lastname: Frank
authors.forename: Mike
authors.initials: M
authors.lastname: Owen
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonetto
authors.forename: Jaana
authors.initials: J
authors.lastname: Suvisaari
authors.forename: Johan Hilge
authors.initials: JH
authors.lastname: Thygesen
authors.forename: Hannes
authors.initials: H
authors.lastname: Pétursson
authors.forename: Jouko
authors.initials: J
authors.lastname: Lönnqvist
authors.forename: Engilbert
authors.initials: E
authors.lastname: Sigurdsson
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Mirella
authors.initials: M
authors.lastname: Ruggeri
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
authors.forename: Olli
authors.initials: O
authors.lastname: Pietiläinen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: David
authors.initials: D
authors.lastname: St Clair
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
chemical_list: C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein