title: GABRB2 in schizophrenia and bipolar disorder: disease association, gene expression and clinical correlations.
abstract: The SCZ (schizophrenia)-associated GABA(A) receptor (gamma-aminobutyric acid type A receptor) beta(2) subunit gene GABRB2 was recently associated with BPD (bipolar disorder). Although weaker than its association with SCZ, significant association of GABRB2 with BPD was found in both German and Chinese, especially for the haplotypes rs1816071-rs187269 and rs1816072-rs187269 for which the M-M variants showed higher frequency in disease than the control. Significant genotype-dependent reduction in GABRB2 expression was shown for BPD, but to a lesser extent than that for SCZ. Temporal effects on GABRB2 expression were observed. Moreover, for the homozygous major genotypes of rs1816071, rs1816072 and rs187269, expression increased with time in CON but decreased in SCZ and BPD. The genotypes of these three SNPs (single nucleotide polymorphisms) were further correlated with antipsychotics dosage in SCZ cohorts. The findings highlight the importance of GABRB2 in neuropsychiatric disease aetiology, with respect to haplotype association, as well as reduction of and temporal effects on gene expression in both SCZ and BPD, but to a lesser extent in the latter, supporting the suggestion that functional psychosis can be conceptualized as a continuous spectrum of clinical phenotypes rather than as distinct categories.
authors.affiliation: Department of Biochemistry and Applied Genomics Center, Fok Ying Tung Graduate School, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, People's Republic of China.
authors.forename: Jianhuan
authors.initials: J
authors.lastname: Chen
authors.forename: Shui-Ying
authors.initials: SY
authors.lastname: Tsang
authors.forename: Cun-You
authors.initials: CY
authors.lastname: Zhao
authors.forename: Frank W
authors.initials: FW
authors.lastname: Pun
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Yu
authors.forename: Lingling
authors.initials: L
authors.lastname: Mei
authors.forename: Wing-Sze
authors.initials: WS
authors.lastname: Lo
authors.forename: Shisong
authors.initials: S
authors.lastname: Fang
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Gerald
authors.initials: G
authors.lastname: Stöber
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
mesh_terms: D044466:Asian People / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C495710:GABRB2 protein, human; D011963:Receptors, GABA-A