18 March 2013. Despite its diminutive moniker, the gene encoding microRNA-137 (MIR137) may pack a punch. According to a study published online March 5 in Molecular Psychiatry, a risk allele in MIR137 contributes to an earlier age of onset in schizophrenia, and to smaller hippocampal volume, larger ventricle volume, and degraded white matter structure in the brains of people with schizophrenia. As these factors are known to vary widely across people with schizophrenia, the findings suggest that MIR137 might account for some of this heterogeneity.
Since its discovery as a genomewide significant hit in schizophrenia (see SRF related news story), researchers have begun to turn the cranks to learn exactly what MIR137 does. MicroRNAs typically fine-tune gene expression, and, indeed, a recent study reports that MIR137 controls expression of several other schizophrenia-related genes (Kwon et al., 2013). The new study, led by James Kennedy and Aristotle Voineskos of the University of Toronto in Canada, examined MIR137 genotypes in 510 people with schizophrenia, and found that those homozygous for the risk allele became ill three years younger than those carrying the non-risk allele. Brain scanning in a smaller sample revealed that risk allele homozygotes with schizophrenia had a smaller left hippocampus, a larger left lateral ventricle, and decreased integrity of white matter compared to non-risk allele carriers with schizophrenia, and to healthy controls. The researchers noted that these effects were not seen in brains of healthy controls homozygous for the risk allele, and suggest that interactions between MIR137 and other schizophrenia risk genes may be needed to give rise to these effects.—Michele Solis.
Lett TA, Chakavarty MM, Felsky D, Brandl EJ, Tiwari AK, Gonçalves VF, Rajji TK, Daskalakis ZJ, Meltzer HY, Lieberman JA, Lerch JP, Mulsant BH, Kennedy JL, Voineskos AN. The genome-wide supported microRNA-137 variant predicts phenotypic heterogeneity within schizophrenia. Mol Psychiatry. 2013 Mar 5. Abstract