Analyzing the Role of MicroRNAs in Schizophrenia in the Context of Common Genetic Risk Variants

IMPORTANCE: The recent implication of 108 genomic loci in schizophrenia marked a great advancement in our understanding of the disease. Against the background of its polygenic nature there is a necessity to identify how schizophrenia risk genes interplay. As regulators of gene expression, microRNAs (miRNAs) have repeatedly been implicated in schizophrenia etiology. It is therefore of interest to establish their role in the regulation of schizophrenia risk genes in disease-relevant biological processes. OBJECTIVE: To examine the role of miRNAs in schizophrenia in the context of disease-associated genetic variation. DESIGN, SETTING, AND PARTICIPANTS: The basis of this study was summary statistics from the largest schizophrenia genome-wide association study meta-analysis to date (83 550 individuals in a meta-analysis of 52 genome-wide association studies) completed in 2014 along with publicly available data for predicted miRNA targets. We examined whether schizophrenia risk genes were more likely to be regulated by miRNA. Further, we used gene set analyses to identify miRNAs that are regulators of schizophrenia risk genes. MAIN OUTCOMES AND MEASURES: Results from association tests for miRNA targetomes and related analyses. RESULTS: In line with previous studies, we found that similar to other complex traits, schizophrenia risk genes were more likely to be regulated by miRNAs (P