title: No evidence for an association between variants at the gamma-amino-n-butyric acid type A receptor beta2 locus and schizophrenia.
abstract: The alpha1/beta2/gamma2-containing heteropentamer is the most abundant gamma-amino-n-butyric acid type A receptor subtype in mammalian brains and the corresponding genes, the GABRA1, GABRB2, and GABRG2 genes, are located in chromosomal region 5q34 that several genome wide scans have implicated as a susceptibility region for schizophrenia. Given this positional and functional evidence, Lo et al. (Mol Psychiatry 2004; 9: 603-608) performed systematic linkage disequilibrium mapping of the GABAAR gene cluster on 5q34 in 130 schizophrenic patients and 170 controls, all of Chinese Han origin. In the single locus and haplotype analyses, single nucleotide polymorphisms in the GABRB2 gene showed highly significant association. The estimated effect caused by GABRB2 varied between odds ratios of 2.27 and 5.12. In order to re-examine their findings, we analyzed the most significantly associated single nucleotide polymorphism in the GABRB2 gene in a sample of 367 patients with schizophrenia and 360 controls, all of German descent. Our sample had a sufficient power to detect the effects described. Neither single marker nor haplotype analysis revealed a significant association with the disease status. Thus, our results do not support the hypothesis that genetic variation at the GABRB2 locus plays a major role in schizophrenic patients of European descent and that such variation would explain the previously observed linkage findings at this chromosomal region.
authors.affiliation: Institute of Human Genetics, Department of Psychiatry, Life & Brain Center, University of Bonn, Bonn, Germany. rami.aboujamra@uni-bonn.de
authors.forename: Rami Abou
authors.initials: RA
authors.lastname: Jamra
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Faten
authors.initials: F
authors.lastname: Dahdouh
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gross
authors.forename: Monika
authors.initials: M
authors.lastname: Deschner
authors.forename: Christine
authors.initials: C
authors.lastname: Schmäl
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
mesh_terms: D001483:Base Sequence; D014644:Genetic Variation; D005838:Genotype; D005858:Germany; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011963:Receptors, GABA-A / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C495710:GABRB2 protein, human; D011963:Receptors, GABA-A