Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8.
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.
Bio-X Life Science Research Center, Shanghai Jiao Tong University, China.
Wu-Yan
WY
Chen
Yong-Yong
YY
Shi
Yong-Lan
YL
Zheng
Xin-Zhi
XZ
Zhao
Guang-Ji
GJ
Zhang
Sheng-Qi
SQ
Chen
Pei-Di
PD
Yang
Lin
L
He
D000217:Acyltransferases / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D002892:Chromosomes, Human, Pair 22; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D012559:Schizophrenia / Q000235:genetics*
D008565:Membrane Proteins; D000217:Acyltransferases; C488097:ZDHHC8 protein, human