Human Molecular Genetics Advance Access originally published online on October 15, 2004
Human Molecular Genetics 2004 13(23):2991-2995; doi:10.1093/hmg/ddh322
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Human Molecular Genetics, Vol. 13, No. 23 © Oxford University Press 2004; all rights reserved
Case–control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8
1Bio-X Life Science Research Center and 2NHGG, Bio-X Center, Shanghai Jiao Tong University, Shanghai, China, 3Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai, China, 4Shanghai Zhabei Institute of Mental Health, Shanghai, China, 5Shanghai Yangpu Institute of Mental Health, Shanghai, China and 6Shanghai Changning Institute of Mental Health, Shanghai, China
Received August 14, 2004; Revised September 19, 2004; Accepted September 29, 2004
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 
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.
* To whom correspondence should be addressed at: Bio-X Center, Shanghai Jiao Tong University, Hao Ran Building, 1954 Hua Shan Road, Shanghai 200030, China. Tel/Fax: +86 2162822491; Email: helin{at}nhgg.org
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