G72/G30 genes and schizophrenia: a systematic meta-analysis of association studies

Abstract

Schizophrenia may result from a neurotransmission hypofunction of glutamatergic and N-methyl-d-aspartate (NMDA) receptors. Linkage disequilibrium mapping has identified several promising and novel positional candidates, including the G72/G30 and d-amino-acid oxidase (DAAO) genes. Since the first positive association report, many subsequent studies have attempted to replicate the association but the results have been mixed. To try to resolve this inconsistency and to elucidate the relationship between the important glutamate-related genes and schizophrenia, the current meta-analysis has combined samples involving 16 polymorphisms covering all published case-control and family-based association studies up to October 2005. The results suggest that there is weak evidence of association between the G72/G30 genes and schizophrenia.

Figure 1.—

Forest plots of ln(OR) with 95% C.I. for the associated polymorphisms of the G72/G30 genes. Solid squares indicate the ln(OR), with the size of the square inversely proportional to its variance, and horizontal lines represent the 95% C.I.'s. The pooled results are indicated by the open diamond.

Figure 2.—

Retrospective analysis of associated polymorphisms was based on publication years since 2002.

Figure 3.—

Representation of the LD structure. The LD structure for the G72/G30 genes, spanning 282 kb, was constructed using genotype data from 108 SNPs. The 12 polymorphisms are shown in green. Vertical tick marks above the name indicate the relative genomic position of each SNP. The LD structure represents the pairwise calculation of D′ for each possible combination of SNPs. D′ < 0.5 is shown in white, D′ = 1.0 in dark red, with increasing shades of red representing increasing D′ among the SNPs. It was produced by Locusview software (T. Petryshen, A. Kirby and M. Ainscow, unpublished results).