MicroRNA: a new frontier in schizophrenia?

A large consortium of researchers in Europe, North American and Australia performed a genome-wide association study (GWAS) of single-nucleotide polymorphisms, which are uncommon variants of genes, among people with schizophrenia in two stages. In the first stage, a discovery analysis of pre-existing GWAS cohorts, they included, 9,394 people with schizophrenia and 12,462 controls, all of European ancestry. In the second-stage independent replication, they used a sample of 8,442 cases and 21,397 controls. In the combined stage-1-and-2 dataset, five alleles had a significant and novel association with schizophrenia, whereas two alleles identified in previous research had significant association. The most robustly newly associated allele was rs1625579 on chromosome 1p21.3, in intron 3 of AK094607. This region codes for the primary transcript of MIR137, a microRNA involved in adult neurogenesis and neuronal maturation. Two previous studies cited in the present report found an association of this regulatory mechanism with schizophrenia. Moreover, four genes identified as possibly associated with schizophrenia in the present study are targets of MIR137.

Although the evidence is circumstantial, the researchers assert a possible pathophysiologic role for the MIR137 mechanism in schizophrenia. Linkage studies, an older approach to identify candidate genes, have identified schizophrenia-related genes such as DISC1, and studies of patients with copy-number variants such as 22q11 deletion syndrome have suggested additional genetic etiologies of psychosis. The heterogeneity of “the group of schizophrenias,” as Bleuler called this disorder (2), is being borne out in genetic research, and psychiatrists should pay attention. We can hope that such work will bear fruit in improved treatments for our patients.

References

1. The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium. Genome-wide association study identifies five new schizophrenia loci. Nat Genet. 2011.18;43:969-976. Full text

2. Bleuler, Eugen. Dementia praecox or the group of schizophrenias. Leipzig, Germany; 1911.