Interactions between Polygenic Risk Scores and Environmental and Epigenomic Background in the Susceptibility and Severity of Mental Disorders

• Grant number: 22/10133-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2022
• End date: April 30, 2025
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Diego Luiz Rovaris
• Grantee: Iago Junger Santos
• 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
• Associated scholarship(s): 24/00083-8 - Epigenetic factors associated with the clinical overlap between Attention Deficit Hyperactivity Disorder and Major Depressive Disorder, BE.EP.IC

Abstract

The great performance of polygenic risk scores (PRS) has already been demonstrated for some physiological variables, such as blood pressure. In the case of mental disorders, several studies have also replicated, in several target samples, the effects of PRSs for schizophrenia, major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), among others. However, most discovery samples are essentially of European ancestry, collected in developed countries, resulting in a Eurocentric and population-homogeneity bias in genomic scanning association studies (GWAS). Because of this, it is extremely important to assess how the environmental and/or epigenomic background of heterogeneous populations with high rates of social inequalities, such as the Brazilian population, mediates or moderates the polygenic effect on the susceptibility and severity of mental disorders. Therefore, the general objective of the project, which is linked to the umbrella project "The Physiological Genomics of Mental Health from the Optical of the Brazilian Exposoma", is to assess how environmental and epigenomic variables modulate the effect of the most studied PRSs in psychiatric biology.