Huang Liang, Ohi Kazutaka, Chang Hong, Yu Hao, Wu Lichuan, Yue Weihua, Zhang Dai, Gao Lei, Li Ming
First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
Department of Neuropsychiatry, Kanazawa Medical University, Ishikawa, Japan.
Am J Med Genet B Neuropsychiatr Genet. 2016 Apr;171B(3):437-46. doi: 10.1002/ajmg.b.32425. Epub 2016 Feb 11.
Common variants in ZNF804A increased the risk of schizophrenia (and bipolar disorder), with low effect sizes in Europeans, which is in line with the polygenic nature of the illnesses, and implies that genetic analyses in small samples may not be sufficient to detect stable results. This notion is supported by the inconsistent replications of ZNF804A variations among individual small Asian samples, indicating the absence of definitive conclusions in this population. We collected psychiatric phenotypic and genetic data from Asian genome-wide association (GWA) and individual replication studies, which include up to 13,452 cases, 17,826 healthy controls, and 680 families, that is, the largest-scale study on ZNF804A in Asian populations to date. The European GWAS risk single nucleotide polymorphism (SNP) rs1344706 was nominally associated with schizophrenia in these Asian samples (one-tailed P = 4.26 × 10(-2) , odds ratio [OR] = 1.048), and the association was further strengthened when bipolar disorder data was also included (one-tailed P = 1.85 × 10(-2) , OR = 1.057). Besides, a non-synonymous SNP rs1366842 in the exon 4 of ZNF804A was also associated with schizophrenia (P = 9.96 × 10(-3) , OR = 1.095). We additionally analyzed other 163 SNPs covering ZNF804A region, but none of them showed any evidence of association. Though the two SNPs did not remain significant if we applied multiple corrections, our analysis should be interpreted as a primary replication study with in prior hypothesis, and rs1344706 and rs1366842 might confer a small but detectable risk of schizophrenia (and bipolar disorder) in Asians. Moreover, the current data suggest the necessity of replication analyses in a large enough scale samples.
ZNF804A基因的常见变异增加了患精神分裂症（和双相情感障碍）的风险，在欧洲人中效应大小较低，这与这些疾病的多基因性质相符，并意味着小样本中的基因分析可能不足以检测到稳定的结果。这一观点得到了亚洲个体小样本中ZNF804A变异不一致重复情况的支持，表明在该人群中尚无定论。我们从亚洲全基因组关联（GWA）和个体重复研究中收集了精神疾病表型和基因数据，这些研究包括多达13452例病例、17826名健康对照和680个家庭，即迄今为止亚洲人群中关于ZNF804A的最大规模研究。欧洲全基因组关联研究（GWAS）中的风险单核苷酸多态性（SNP）rs1344706在这些亚洲样本中与精神分裂症呈名义上的关联（单尾P = 4.26×10⁻²，优势比[OR]=1.048），当纳入双相情感障碍数据时，这种关联进一步增强（单尾P = 1.85×10⁻²，OR = 1.057）。此外，ZNF804A外显子4中的一个非同义SNP rs1366842也与精神分裂症相关（P = 9.96×10⁻³，OR = 1.095）。我们还分析了覆盖ZNF804A区域的其他163个SNP，但它们均未显示出任何关联证据。尽管如果进行多重校正，这两个SNP不再显著，但我们的分析应被解释为一项具有先验假设的初步重复研究，并且rs1344706和rs1366842可能在亚洲人中赋予了小但可检测到的精神分裂症（和双相情感障碍）风险。此外，当前数据表明在足够大规模的样本中进行重复分析的必要性。
