Background
Single nucleotide polymorphisms (SNPs) and haplotypes in intron 8 of type A γ-aminobutyric
acid (GABAA) receptor β2 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.
Key Words
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Article info
Publication history
Published online: September 04, 2006
Accepted:
May 9,
2006
Received in revised form:
May 3,
2006
Received:
March 21,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
