CORRELATION ANALYSIS OF miRNA AND mRNA EXPRESSION PROFILES IN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM ADHD PATIENTS AND CONTROLS

Background Attention Deficit Hyperactivity Disorders (ADHD) is a neurodevelopmental disorder characterized by impairment in sustaining attention and inability to control impulses and modulate activity level. The aetiology of ADHD is complex, involving genetic and environmental factors, with an estimated heritability of 70–80%. Nevertheless, inconsistencies in the results of the genetic studies on ADHD may be explained, in part, by epigenetic mechanisms such as microRNAs (miRNAs) which play important roles in the control of gene expression by pairing to target mRNAs. Under the hypothesis that alterations in the processing or target binding of miRNAs may result in differential mRNA expression profiles predisposing to ADHD, we performed mRNA and miRNA expression profiling in Peripheral Blood Mononuclear Cells (PBMCs) of 103 persistent ADHD individuals and 115 controls. Methods miRNA and mRNA expression profiling in PBMCs of 103 ADHD patients and 115 controls were assessed by high-throughput deep sequencing (HiSeq. 2000, Illumina) and the Human Gene 1,1 ST microarray (Affymetrix), respectively. The analyses of differential expression for miRNA and mRNA were carried out separately applying Linear Model Fit using the Limma R package. ROC curves were used to evaluate the accuracy of the differentially expressed miRNAs in discriminating patients with ADHD from controls in an independent sample of 46 cases and 46 controls. In order to build miRNA-mRNA interaction networks that may be relevant to ADHD, including positive and negative relationships, we integrated the expression data of miRNAs and mRNAs differentially expressed in ADHD (adjusted p-values Results After quality control, normalization and background correction, a total of 573 miRNAs and 19,784 transcripts were included in the analysis. We identified a total of 79 miRNAs and 1,592 transcripts differentially expressed in ADHD when compared to controls. Of them, miR-191-5p and miR-23a-5p showed values of AUC > 0.70 in the test sample; they were selected for the subsequent correlation analysis. Evidence for 126 miRNA-mRNA pairs was found (p Discussion In conclusion, our findings provide for the first time tentative evidence for the contribution of miR-23a-5p - OCIAD2 correlated network to ADHD etiology through a comprehensive differentially expression analysis of miRNA and mRNA in PMBCs.