Meta-analysis indicates that the European GWAS-identified risk SNP rs1344706 within ZNF804A is not associated with schizophrenia in Han Chinese population

PLoS One. 2013 Jun 12;8(6):e65780. doi: 10.1371/journal.pone.0065780. Print 2013.

Abstract

Recent genetic association studies have implicated several candidate susceptibility variants for schizophrenia among general populations. Rs1344706, an intronic SNP within ZNF804A, was identified as one of the most compelling candidate risk SNPs for schizophrenia in Europeans through genome-wide association studies (GWASs) and replications as well as large-scale meta-analyses. However, in Han Chinese, the results for rs1344706 are inconsistent, and whether rs1344706 is an authentic risk SNP for schizophrenia in Han Chinese is inconclusive. Here, we conducted a systematic meta-analysis of rs1344706 with schizophrenia in Chinese population by combining all available case-control samples (N = 12), including a total of 8,982 cases and 12,342 controls. The results of our meta-analysis were not able to confirm an association of rs1344706 A-allele with schizophrenia (p = 0.10, odds ratio = 1.06, 95% confidence interval = 0.99-1.13). Such absence of association was further confirmed by the non-superiority test (p = 0.0003), suggesting that rs1344706 is not a risk SNP for schizophrenia in Han Chinese. Detailed examinations of individual samples revealed potential sampling bias in previous replication studies in Han Chinese. The absence of rs1344706 association in Han Chinese suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating genome-wide association findings of schizophrenia across different ethnic populations.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Regression Analysis
  • Schizophrenia / genetics*

Substances

  • Kruppel-Like Transcription Factors
  • ZNF804A protein, human

Grants and funding

This work was supported by grants from the National 973 project of China (grant numbers, 2011CBA00401) and the National Natural Science Foundation of China (U1202225, 31130051 and 31071101). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.