ZNF804A and schizophrenia susceptibility in Asian populations.
ZNF804A, a recently identified risk gene for schizophrenia, has been extensively investigated and the principle finding for this locus has been the association with SNP rs1344706 in populations of European ancestries. However, in Asian populations, only a few studies have been conducted for rs1344706 and the results were inconsistent. Here, we studied rs1344706 and schizophrenia susceptibility in multiple Asian case-control samples (10 Chinese and 2 Japanese samples; N = 21,062), and the meta-analyses indicated non-significant association of rs1344706 with schizophrenia (P = 0.26), suggesting the same SNP identified in European samples is not predisposing risk in Asians. Further genotyping and association analyses of a set of SNPs spanning the entire genomic region of ZNF804A (520 kb) identified no association except for SNP rs359895 (P = 7.8 x 10(-5) , N = 5,172), a newly reported risk SNP located in the ZNF804A promoter region with functional implications. This suggests that ZNF804A may also contribute to schizophrenia susceptibility in Asians although the risk SNP is different from that in Europeans, and it was supported by the detected up-regulation of ZNF804A mRNA expression in the blood cells of Chinese schizophrenia patients compared with normal controls (P = 0.004). Additionally, the linkage disequilibrium (LD) structure analyses using data from HapMap indicated distinct LD blocks across ZNF804A between Chinese and Europeans, which may explain the different association patterns between them, and also highlight the compounding difficulty of genetic studies of complex diseases like schizophrenia when studying multiple ethnic populations.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Ming
M
Li
Cui-Juan
CJ
Shi
Yong-Yong
YY
Shi
Xiong-Jian
XJ
Luo
Xue-Bin
XB
Zheng
Zhi-Qiang
ZQ
Li
Jian-Jun
JJ
Liu
Siow-Ann
SA
Chong
Jimmy
J
Lee
Yi
Y
Wang
Xing-Yan
XY
Liu
Li-De
LD
Yin
Xing-Fu
XF
Pu
Hong-Bo
HB
Diao
Qi
Q
Xu
Bing
B
Su
D044466:Asian People / Q000235:genetics / Q000523:psychology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000208:ethnology* / Q000235:genetics*; D015854:Up-Regulation; D044465:White People
D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human