Association study of schizophrenia with variants in miR-137 binding sites.

There is strong cumulative evidence for the involvement of miR-137 and its targets in the aetiology of schizophrenia. Here we test whether variants, especially rare variants, in miR-137 binding sites are associated with schizophrenia in an exome-sequenced sample of 4225 cases and 5834 controls. Only a small proportion of binding sites were covered by the capture system which had been used. A weighted burden test using the 372 detected variants demonstrated an excess among cases significant at p=0.024. The sample size is too small to implicate individual variants or genes but overall this finding does provide some further support for the hypothesis that disruption of miR-137 binding sites can increase the risk of schizophrenia, perhaps by leading to over-expression of the target gene. We recommend that future exome sequencing studies should cover the untranscribed regions of genes, which contain the microRNA binding sites, in order that this potentially important pathogenic mechanism can be adequately investigated.