GABRB2 association with schizophrenia: commonalities and differences between ethnic groups and clinical subtypes.
BACKGROUND
Single nucleotide polymorphisms (SNPs) and haplotypes in intron 8 of type A gamma-aminobutyric acid (GABA(A)) receptor beta2 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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lo
Wing-Sze
WS
Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science and Technology, Hong Kong, China.
Harano
Mutsuo
M
Gawlik
Micha
M
Yu
Zhiliang
Z
Chen
Jianhuan
J
Pun
Frank W
FW
Tong
Ka-Lok
KL
Zhao
Cunyou
C
Ng
Siu-Kin
SK
Tsang
Shui-Ying
SY
Uchimura
Naohisa
N
Stober
Gerald
G
Xue
Hong
H
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000208:ethnology; D006801:Humans; D007438:Introns; D007564:Japan / Q000208:ethnology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011963:Receptors, GABA-A / Q000235:genetics*; D012559:Schizophrenia / Q000145:classification* / Q000235:genetics*
C495710:GABRB2 protein, human; D011963:Receptors, GABA-A