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Genetic variants in the 22q11 gene ZDHHC8, which encodes a putative transmembrane palmitoyltransferase, has been associated to schizophrenia in family-based linkage disequilibrium (LD) studies. The single nucleotide polymorphism (SNP) rs175174 (A/G), which had the strongest association, has been shown recently to regulate the level of the fully functional transcript by modulating the retention of intron 4 of ZDHHC8. In this work, we genotyped three genetic variants within the ZDHHC8 locus and conducted association studies in both population- and family-based samples of the Han Chinese population. The three polymorphisms spanning approximately 5.5 Kb were detected to be in significant LD. Our results provided compelling supportive evidence for association of the variants within the ZDHHC8 locus with schizophrenia but revealed different risk allele at SNP rs175174. The G allele was significantly more common in cases than in controls (69.47 : 59.96%; P=0.000018) and excess transmission of the same allele was confirmed in the family-based transmission disequilibrium test (transmitted/non-transmitted=87 : 54; P=0.0055). Both sample sets even shared the same risk haplotype with similar frequency. Our current data presents consistent association results obtained from both case-control and family-based samples in a same laboratory under the same experimental condition. Despite the potential genetic heterogeneity, our independent findings further support that the 22q11 region is likely to harbor candidate schizophrenia susceptibility genes.

human molecular genetics online/human molecular genetics

Case–control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8