MicroRNAs and Target Site Screening Reveals a Pre-microRNA-30e Variant Associated with Schizophrenia

MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the stability and translation of mRNA targets. Increasing evidence suggests that miRNAs could be involved in the initiation and progression of neuropsychiatric disorders. Prior to this study, six miRNAs had been reported to show a significantly abnormal expression level in schizophrenic brains. Also, common single nucleotide polymorphisms within two miRNA transcripts have shown genetic associations with schizophrenia. However, it remains largely unknown whether variants in these miRNA genes and/or in their target sites are associated with schizophrenia. Here, we selected the above eight miRNAs, plus 15 of their experimentally validated target sites, as candidate susceptibility factors for schizophrenia, for mutation screening and further association studies in Chinese case-control samples. We identified a new potentially functional variant ss178077483 located in the pre-mir-30e, which was strongly associated with schizophrenia (allelic P=0.00017; genotypic P=0.00015), with an odds ratio of 4.952 (95% confidence interval: 1.887-12.998). We also demonstrated that this new variant ss178077483, combined with mir-30e rs7556088 and mir-24-MAPK14 rs3804452, showed a weak gene-gene interaction for schizophrenia risk (P=0.001). In addition, analysis of gene expression demonstrated that expression of the mature mir-30e in the peripheral leukocytes was significantly higher in patients' group than in the control group (P=6.79e-7).This is the first study to indicate that mir-30e ss178077483 plays a role in schizophrenia susceptibility. It suggests that the contribution of mir-30e to the processes that lead to schizophrenia should be further investigated.