Association between NR4A2 genetic variation and schizophrenia: A comprehensive systematic review and meta-analysis

• Comprehensively quantified the impact of all the reported variants of NR4A2 on schizophrenia risk.
• Summarized all the genotype distribution of NR4A2 variants and made a comprehensive meta-analysis of three SNPs in case-control studies.
• Five variants of NR4A2 were present only in cases.
• Failed to reveal significant association between NR4A2 variation and SZ risk.

The homo sapiens nuclear receptor subfamily 4, group A (NR4A2) genetic variation has been implicated as a risk factor for schizophrenia (SZ). Nevertheless, the results are inconclusive. We conducted a comprehensive systematic review and meta-analysis to quantify the impact of NR4A2 variation on the risk of SZ. All eligible case-control studies published up to September 2014 were identified by searching PubMed OVID, EBSCO, PsycINFO and ISI web of knowledge. Pooled odds ratio with 95% confidence interval were used to access the strength of association in fixed- or random-effects model. Seven studies that reported 17 variants with a total of 3027 participants were included. Of these variants, five ones (rs143618355, rs199674295, c.366-369 del TAC, c.-469delG and P4) were present only in cases, and three ones (rs35479735, rs3832066 and rs397706674) were available for meta-analysis. Overall, there was no significant association between the three variants and SZ risk under allele model, dominant model and recessive model. The results failed to reveal significant link between NR4A2 polymorphism and SZ risk. However, large-sized and well-designed studies are warranted to validate our findings.