title: DRD4 VNTR polymorphism and age at onset of severe mental illnesses.
abstract: A large number of studies has investigated the hypothesis that DRD4 48 bp variable number of tandem repeat (VNTR) polymorphism is involved in the etiology of schizophrenia and bipolar disorder. However, the results are inconsistent likely due to genetic and phenotypic heterogeneity. Age at onset (AAO) is considered an important alternate phenotype for genetic investigations of psychiatric disorders. In the present study, the DRD4 VNTR 7 repeat allele (7R) was examined in 477 patients with major psychoses. Age at onset was defined as the age of first psychotic episode for schizophrenia and the age at appearance of first clinically recognized symptoms for the bipolar sample. Our results showed an interaction between sex and DRD4 genotypes among schizophrenia patients (n=203, β=.213, p=.017). On comparing AAO between carriers and non-carriers of the 7R, we observed that females with 7R present had later onset (p=.021). The effect was not observed for males. In the sample with bipolar disorder, we observed significant association between DRD4 7R-genotype and AAO (n=274, β=-.148, p=.012). No interaction was observed between sex and genotypic groups of the bipolar sample. The 7R was associated with early onset of the bipolar illness (p=.028). In summary, our results suggest that the 7R is associated with AAO in both schizophrenia and bipolar disorders. The effect was observed across both sexes in bipolar disorder, but specifically in females for schizophrenia.
authors.affiliation: Neurogenetics Section, Neuroscience Department, Centre for Addiction and Mental Health, Toronto, ON, Canada. vanessa deoliveira@camh.net
authors.forename: Vanessa Faria
authors.initials: VF
authors.lastname: Gonçalves
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Vincenzo
authors.initials: V
authors.lastname: de Luca
authors.forename: Say Li
authors.initials: SL
authors.lastname: Kong
authors.forename: Clement
authors.initials: C
authors.lastname: Zai
authors.forename: Maria
authors.initials: M
authors.lastname: Tampakeras
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Mackenzie
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D017677:Age Distribution; D017668:Age of Onset; D001714:Bipolar Disorder / Q000453:epidemiology* / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: C493599:DRD4 protein, human; D005819:Genetic Markers; D050638:Receptors, Dopamine D4