Mendelian randomization reveals the causal links between microRNA and schizophrenia

Abstract

MicroRNAs have pivotal roles in gene regulation. However, microRNAs that have causal effects on schizophrenia remain largely unknown. To investigate the causal relationships between microRNAs and schizophrenia, here we conduct a Mendelian randomization (MR) study. The genome-wide association study (GWAS) of schizophrenia (67,390 cases and 94,015 controls) from PGC3 were used as the outcome. Genetic variants associated with microRNAs were used as exposure in MR analysis. We identified 6 microRNAs that showed causality on schizophrenia. These microRNAs include hsa-miR-570–3p (OR = 1.03, 95% confidence interval (CI): 1.02 to 1.05, P = 5.45 × 10−5), hsa-miR-550a-3p (OR = 1.12, 95% CI: 1.06 to 1.18, P = 5.99 × 10−5), hsa-miR-130a-3p (OR = 1.10, 95% CI: 1.05 to 1.15, P = 1.58 × 10−4), hsa-miR-210 (OR = 0.87, 95% CI: 0.82 to 0.93, P = 3.09 × 10−5), hsa-miR-337–3p (OR = 1.01, 95% CI: 1.01 to 1.02, P = 3.39 × 10−4), and hsa-miR-130b-3p (OR = 0.89, 95% CI: 0.84 to 0.94, P = 1.50 × 10−5). Differential expression analysis showed dysregulation of hsa-miR-130b-3p in schizophrenia cases compared with controls. Gene Ontology (GO) analysis showed that the targets of these causal microRNAs were significantly enriched in RNA splicing pathways. This MR study identified six microRNAs whose genetically regulated expression might have a causal role in schizophrenia, indicating the causality of these microRNAs in schizophrenia. Our findings also indicate that these microRNAs may be used as potential biomarkers for schizophrenia.