The α1/β2/γ2-containing heteropentamer is the most abundant γ-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.
aInstitute of Human Genetics
bInstitute for Medical Biometry, Informatics and Epidemiology
cDepartments of Psychiatry
dGenomics, Life & Brain Center, University of Bonn, Bonn
eInstitute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg
fCentral Institute of Mental Health, Division Genetic Epidemiology in Psychiatry, Mannheim, Germany
Correspondence and requests for reprints to Dr Rami Abou Jamra, MD, Institute of Human Genetics, University of Bonn, Wilhelmstr. 31, D-53111 Bonn, Germany
Tel: +49 228 287 22170; Fax: +49 228 287 22630; e-mail: firstname.lastname@example.org
Sponsorship: This study was supported by the National Genomic Network (NGFN) of the German Ministry of Education and Research, the SFB 400 of the German Research Council (DFG), the Fund for Scientific Research Flanders (FWO, grants G.0425.02 and G0438.03), the Belgium Interuniversity Attraction Pole (IUAP ‘molecular genetics and cell biology’), and a Concerted Research Project (GOA) by the University of Antwerp. T. B. was supported by grant KN 378/1-1 (Project D1 of FOR 423) of the German Research Council (DFG).
Received 14 August 2006 Accepted 15 August 2006