Testing for genetic association between the ZDHHC8 gene locus and susceptibility to schizophrenia: An integrated analysis of multiple datasets.

A number of studies have reported an association between the ZDHHC8 gene locus and schizophrenia but have produced some divergent findings and their interpretation is not straightforward. We investigated the association of the ZDHHC8 gene locus with schizophrenia using meta-analytic techniques, combining all published data up to May 2009 and focusing on 10 independent studies from six published references covering 2,894 cases, 2,932 controls and 1,225 parent-offspring trios. We restricted the analysis to studies investigating rs175174, the most frequently studied single nucleotide polymorphism (SNP). Stratified meta-analysis was conducted to investigate whether ancestry, study design, or gender moderated any association. Analyses of linkage disequilibrium (LD) and haplotype structure of this gene locus were also performed based on the hapmap project genotype data to determine whether there were other independent polymorphic markers which might contribute to susceptibility to schizophrenia in particular ethnic populations. We found no allelic- or genotype-wise evidence for an association of the rs175174 SNP with schizophrenia in our overall analysis. After applying stratified analyses, there was only a weak nominal genotype-wise association of this SNP with schizophrenia in the dominant genetic model in East Asian populations (P = 0.049), which might be caused by significant between-study heterogeneity (P = 0.042). No significant publication bias was detected. Other polymorphic markers within this gene genotyped in the hapmap project across different ethnic populations were in strong LD with rs175174. Consistently negative associations were found in the rs175174 polymorphism. LD structure further suggested that the ZDHHC8 locus might not play an important role in the etiology of schizophrenia.