ANALYSIS OF THE BIOLOGICAL CONNECTION BETWEEN IRON METABOLISM MARKERS AND ATTENTION DEFICIT HYPERACTIVITY DISORDER

• Grant number: 24/18586-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Diego Luiz Rovaris
• Grantee: Thales Vieira Rodrigues
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Iron plays a crucial role in the development and proper function of the brain, especially in cognitive functions such as attention and memory. Evidence suggests that its deficiency during development is associated with neuropsychiatric disorders, including Attention Deficit Hyperactivity Disorder (ADHD). Genome-wide association studies (GWAS) are important tools for identifying genetic variants and biological pathways associated with a specific phenotype, such as ADHD or levels of iron markers, and they serve as a basis for various post-GWAS methodologies, such as polygenic score (PGS) calculations and genetic correlations between phenotypes of interest. This project builds on a completed project in which the student investigated the association between iron metabolism markers and ADHD through PGS calculations. In this project, new methodologies will be incorporated to dissect pleiotropy between ADHD and iron markers, specifically: Bivariate Causal Mixture Model (MiXeR), Local Analysis of [co]-Variant Annotation (LAVA), and Gene Set Enrichment Analysis (GSEA). While the PGS measures the relative risk an individual has of developing certain traits/diseases based on their genomic composition, MiXeR and LAVA calculate global and local genetic correlations between two phenotypes, respectively. These tools are essential for evaluating the relationships between two traits of interest, helping to understand the existence of shared biological mechanisms underlying each pair of phenotypes. From this perspective, the project aims to deepen the hypothesis that the genetic control involved in iron biology and metabolism is related to the development and/or clinical presentation of ADHD.