Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• microRNA-137 (miR-137) is implicated in schizophrenia's genetic underpinnings.
• MIR137HG risk variants affect brain imaging measures, and miR-137 regulates numerous genes.
• Previous research identified schizophrenia risk in miR-137-regulated gene sets.

Purpose of the Study:

• To investigate the combined effect of a MIR137HG risk variant and miR-137-regulated genes on gray matter concentration (GMC) in schizophrenia.
• To explore the interaction between genetic risk, diagnosis, and GMC patterns.

Main Methods:

• Genotyping of the MIR137HG risk variant (rs1625579) and variants in TCF4, PTGS2, MAPK1, and MAPK3 in 221 Caucasian subjects (89 patients, 132 controls).
• Calculation of a genetic risk score (GRS) for miR-137-regulated genes.
• Multivariate analysis assessing three-way interaction between rs1625579 genotype, GRS, and diagnosis on GMC.

Main Results:

• Schizophrenia patients homozygous for the MIR137HG risk allele showed decreased occipital, parietal, and temporal lobe GMC with increasing GRS.
• Schizophrenia patients with the protective MIR137HG allele showed increased GMC with increasing GRS.
• No significant correlations between GMC and GRS were observed in control subjects.

Conclusions:

• Genetic variants in miR-137-regulated genes, along with the MIR137HG risk variant, may influence GMC in schizophrenia-related brain regions.
• Dysregulation of protein kinase A signaling due to altered miR-137 biogenesis could contribute to gray matter loss in schizophrenia.