Epigenetic aspects involved in ADHD and related phenotypes

• Grant number: 23/12252-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2024
• End date: November 30, 2024
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Diego Luiz Rovaris
• Grantee: Cibele Edom Bandeira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/05652-0 - The physiological genomics of mental health from the perspective of the Brazilian exposome, AP.JP

Abstract

Although the total heritability of ADHD is estimated at H 80%, the proportion of phenotypic variability explained by common genome variability is only 14% (SNP heritability). This demonstrates that other biological components play an important role in ADHD. Epigenetic mechanisms, which operate at the intersection of individuals' genomic and environmental contexts, are important candidates for explaining fractions of ADHD's phenotypic variance. In this sense, DNA methylation can serve as a marker for the risk of development and the clinical course of the disorder. There are few epigenome-wide association studies (EWAS) conducted on ADHD, especially in samples of adult individuals. Therefore, this project aims to help fill this gap by examining the relationship between DNA methylation and ADHD in adults, as well as related phenotypes. In this project, we plan to analyze already collected EWAS data from two samples: one case-control (n = 380) and another population-based sample with measures of ADHD symptoms (n = 650). They are part of the ADHD Outpatient Program at the Hospital de Clínicas de Porto Alegre (PRODAH) and have already undergone extensive data collection (genome-wide data, structural and functional neuroimaging, clinical, and demographic protocols). Additionally, a new independent sample is being collected by the group (n = 300) in São Paulo. From these datasets, we will assess the role of methylation scores and epigenetic clocks as potential biological markers for ADHD and its clinical course. Through this project, it will be possible to gain insights into relevant epigenetic markers associated with ADHD within the Brazilian context (exposome).