title: A dysbindin risk haplotype associated with less severe manic-type symptoms in psychosis.
abstract: Delineating relationships between susceptibility genes and clinical symptoms may be an important step in understanding the genetics of psychosis. Recent data suggests that the gene dysbindin (DTNBP1) may confer susceptibility across psychotic disorders and may particularly be associated with negative symptoms, i.e. affective flattening, alogia and avolition. We have previously published evidence of association with a dysbindin risk haplotype derived from alleles C-A-T at SNPs P1655 (rs2619539), P1635 (rs3213207) and SNP66961 (rs2619538) in two independent schizophrenia (SZ) case-control samples. The C-A-T haplotype impacts at the level of gene function and phenotype: the haplotype indexes lower cortical expression of the dysbindin gene in post-mortem SZ brain samples and haplotype carriers show greater deficits in spatial working memory and early visual processing than non-carrier SZ patients. The aim of this study was to establish if the C-A-T dysbindin risk haplotype is associated with a specific clinical symptom profile. We investigated the relationship between the haplotype and PANSS-derived symptom factors in 262 individuals with schizophrenia/schizoaffective disorder using principal components analysis (PCA) and analysis of variance (ANOVA). Dysbindin risk carriers scored significantly less than non-carriers on the 'hostility/excitability' factor (F 1,196=8.468; p=.004), with a trend for higher negative symptom scores. This suggests that risk variation at the dysbindin gene may contribute to a more prototypical SZ presentation with less severe excitement/manic symptoms and more negative symptoms.
authors.affiliation: Neuropsychiatric Genetics Group, Institute of Molecular Medicine, Trinity College Dublin, St. James Hospital, Dublin 8, Ireland. acorvin@tcd.ie
authors.forename: Aiden
authors.initials: A
authors.lastname: Corvin
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
authors.forename: Jeanne Marie
authors.initials: JM
authors.lastname: Nangle
authors.forename: Siobhan
authors.initials: S
authors.lastname: Schwaiger
authors.forename: Derek
authors.initials: D
authors.lastname: Morris
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000209:etiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins