Methylomic changes during development of psychiatric disorders

Abstract

Psychiatric disorders are genetically complex traits. Despite decades of research, there is little certainty about their biological basis. The study of basic dimensions of functioning (psychiatric symptoms) instead of psychiatric diagnosis could help to better understand the nature of these disorders. In the present study, we aim: 1) to compare genome-wide DNA methylation in peripheral blood of children and adolescents with low psychiatric symptoms (PS) at baseline and with high PS after 3 years of follow-up (categorical comparison); 2) to identify methylation changes associated to symptoms of psychiatric disorders (continuous comparison); 3) to identify methylation changes associated to environmental risk factors experienced by the subjects during 3 years of follow-up; 4) to verify if the genes located near differentially methylated regions present differentially expression patterns; and 5) to learn how to perform and analyze big data from DNA methylation microarray and gene expression microarray using bioinformatics tools. In this way, we will investigate subjects from a large prospective community school-based study in Brazil, the High Risk Cohort (HRC) for Psychiatric Disorders. The HRC has clinical and genetic measures in two different time-points (baseline and 3 years of follow-up). In both points, PS were assessed using Child Behavior Checklist (CBCL). For the present study, we will select from HRC 24 subjects with CBCL score < 30 at the baseline that increased these score more than 16 (mean = 29, SD = 9) after 3 years of follow-up. We will generate methylation data using the Infinium Methylation EPIC BeadChip. DNA methylation microarray and all the analyses and the bioinformatics training will be developed in collaboration with Dr. Hakon Hakonarson group, in the Center for Applied Genomics at Children's Hospital of Philadelphia. To execute our 4th aim, we will use the data generated by other project from our group also supported by FAPESP (FAPESP Nº 2017/05339-7). The results of this study may contribute to a better understanding of the pathogenesis of psychiatric disorder in children and adolescents. (AU)