Identification in 2 independent samples of a novel schizophrenia risk haplotype of the dystrobrevin binding protein gene (DTNBP1)

Nigel Melville Williams, Anna Preece, DW Mortis, Gillian Spurlock, Nicholas John Bray, M Stephens, N Norton, H Williams, M Clement, S Dwyer, C Curran, J Wilkinson, Valentina Escott-Price, JL Waddington, M Gill, AP Corvin, Stanley Zammit, George Kirov, Michael John Owen, Michael Conlon O'Donovan

Research output: Contribution to journalArticle (Academic Journal)

155 Citations (Scopus)

Abstract

Context Recent research suggests that variation in the gene encoding dystrobrevin binding protein (DTNBP1) confers susceptibility to schizophrenia. Thus far, no specific risk haplotype has been identified in more than 1 study. Objectives To confirm DTNBP1 as a schizophrenia susceptibility gene, to identify and replicate specific risk and protective haplotypes, and to explore relationships between DTNBP1 and the phenotype. Design Genetic association study based on mutation detection and case-control analysis. Setting All subjects were unrelated and ascertained from general (secondary care) psychiatric inpatient and outpatient services. Participants The Cardiff, Wales, sample included 708 white subjects from the United Kingdom and Ireland (221 females) who met DSM-IV criteria for schizophrenia and were individually matched for age, sex, and ethnicity to 711 blood donor controls (233 females). Mean $ SD age at first psychiatric contact for cases was 23.6 $ 7.7 years; mean age at ascertainment was 41.8 $ 13.5 years. The Dublin, Ireland, sample included 219 white subjects from the Republic of Ireland who met DSM-III-R criteria for schizophrenia or schizoaffective disorder and 231 controls. The mean age of the Irish cases was 46.0 $ 8.5 years; mean age at first psychiatric contact was 25.2 $ 12.4 years. Main Outcome Measure Evidence for association between the DTNBP1 locus and schizophrenia. Results In the Cardiff sample, there was no evidence for association with previously implicated haplotypes but strong evidence for association with multiple novel haplotypes. Maximum evidence was found for a novel 3-marker haplotype (global P
Original languageEnglish
Pages (from-to)336-344
Number of pages9
JournalArchives of General Psychiatry
Volume61
Issue number4
DOIs
Publication statusPublished - 1 Apr 2004

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