No Association Between the Putative Functional ZDHHC8 Single Nucleotide Polymorphism rs175174 and Schizophrenia in Large European Samples

It has been recently reported that a functional variant in the ZDHHC8 gene encoding a putative palmitoyltransferase directly confers susceptibility to schizophrenia in females ( Mukai et al 2004). We investigated the putative risk allele (rs175174) in four schizophrenia association samples including a Bulgarian proband and parent sample (474 trios) and three case-control panels of European origin (1028 patients/1253 control subjects) in an attempt to replicate these findings. Our results do not support the hypothesis that genetic variation at rs175174 is associated with increased risk for schizophrenia nor do they suggest the presence of gender-specific differences. Our data suggest that the reported genetic association by Mukai et al either represents type I error resulting from sampling variance or that rs175174 is in linkage disequilibrium (LD) with the functional variant for schizophrenia and different LD patterns obscure the detection of association.