GABRB2 Association with Schizophrenia: Commonalities and Differences Between Ethnic Groups and Clinical Subtypes

• Published in: Biological psychiatry (1969) Vol. 61; no. 5; pp. 653 - 660
• Main Authors: Lo, Wing-Sze, Harano, Mutsuo, Gawlik, Micha, Yu, Zhiliang, Chen, Jianhuan, Pun, Frank W., Tong, Ka-Lok, Zhao, Cunyou, Ng, Siu-Kin, Tsang, Shui-Ying, Uchimura, Naohisa, Stober, Gerald, Xue, Hong
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2007; Elsevier Science
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Biological and medical sciences; Case-Control Studies; Complex disease; Ethnic Groups; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Germany - ethnology; haplotype; Humans; Introns; Japan - ethnology; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; population association; psychiatric disorder; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Receptors, GABA-A - genetics; Schizophrenia; Schizophrenia - classification; Schizophrenia - genetics; SNP; Japan; Germany; psychiatric disorder; population association; haplotype; Complex disease; SNP; Psychosis; Schizophrenia; Mental disorder; Genetics; Genetic determinism; Haplotype; Ethnic group
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.05.003

Single nucleotide polymorphisms (SNPs) and haplotypes in intron 8 of type A γ-aminobutyric acid (GABA A) receptor β 2 subunit gene (GABRB2) were initially found to be associated with schizophrenia in Chinese. This finding was subjected to cross-validation in this study with Japanese (JP) and German Caucasian (GE) subjects. Single nucleotide polymorphisms discovery and genotyping were carried out through resequencing of a 1839 base pair (bp) region in GABRB2. Tagging SNPs (tSNPs) were selected based on linkage disequilibrium (LD), combinations of which were analyzed with Bonferroni correction and permutation for disease association. Random resampling was applied to generate size- and gender-balanced cases and control subjects. Out of the 17 SNPs (9.2/kilobase [kb]) revealed, 6 were population-specific. Population variations in LD were observable, and at least two low LD points were identified in both populations. Although disease association at single SNP level was only shown in GE, strong association was demonstrated in both JP ( p = .0002 – .0191) and GE ( p = .0033 – .0410) subjects, centering on haplotypes containing rs1816072 and rs1816071. Among different clinical subtypes, the most significant association was exhibited by systematic schizophrenia. Cross-population validation of GABRB2 association with schizophrenia has been obtained with JP and GE subjects, with the genotype-disease correlations being strongest in systematic schizophrenia, the most severe subtype of the disease.