title: ANK3, CACNA1C and ZNF804A gene variants in bipolar disorders and psychosis subphenotype.
abstract: OBJECTIVES. The ANK3, CACNA1C and ZNF804A genes have been implicated in both bipolar disorders (BPD) and schizophrenia (SCZ). It has been suggested that BPD with psychosis may be a clinical manifestation of genes overlapping between BPD and SCZ. We therefore tested the association of these genes with BPD in a large family-based sample, and then dissected the phenotype into psychosis present or absent subgroups. METHODS. We genotyped four high interest single nucleotide polymorphisms from ANK3 (rs10994336, rs9804190), CACNA1C (rs1006737), and ZNF804A (rs1344706). Family based association testing (FBAT) was performed on 312 families, and within psychotic (N = 158) and non-psychotic BPD (N = 119) subgroups. RESULTS. In the whole sample, we found a nominal association in ZNF804A (rs1344706, P = 0.046), and a trend in CACNA1C (rs1006737, P = 0.077). In the psychotic BPD subgroup, as hypothesized, stronger signals were observed in ZNF804A (P = 0.019) and CACNA1C (P = 0.017). We found no association in the ANK3 markers, but the rs10994336 variant was nominally associated with non-psychotic BPD (P = 0.046). Exploratory analysis revealed the rs1344706 variant was also implicated in suicide-attempt behaviour (P = 0.038). CONCLUSIONS. These tentative results are consistent with the hypothesis that the subphenotype of BPD with psychosis may represent a clinical manifestation of shared genetic liability between BPD and SCZ.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Tristram A P
authors.initials: TA
authors.lastname: Lett
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Sajid A
authors.initials: SA
authors.lastname: Shaikh
authors.forename: Olga
authors.initials: O
authors.lastname: Likhodi
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000328:Adult; D000483:Alleles; D017487:Ankyrins / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011618:Psychotic Disorders / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins; C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human