Association between Genomic Variants and Psychiatric Disorders, Functional Deviations and Age of Onset

• Grant number: 24/06577-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2024
• Effective date (End): December 31, 2024
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Jair de Jesus Mari
• Grantee: Celina Huey Oshiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/12901-9 - National Center for Research and Innovation in Mental Health (CISM), AP.ESP

Abstract

Introduction: Mental disorders are one of the main causes of disability and dysfunctional trajectories in developed countries, causing great harm to the individual, their family and society. These disorders are considered to be multifactorial diseases, in which genetic factors (both low effect, such as single nucleotide variants - SNVs, and high effect, such as copy number variations - CNVs) and environmental factors interact and can lead to their development. In recent years, genome-wide association studies (GWAS) have enabled a greater understanding of the molecular mechanisms of mental disorders. However, the biological mechanisms underlying this genetic susceptibility are still unclear. Objective: This study aims to associate genomic variants (SNVs and CNVs) with the presence of mental disorders, as well as with functional deviations during the 6-year follow-up (in the third follow-up and phase 2 of the thematic project - age group at higher risk of involvement) of the Brazilian High Risk Cohort for psychiatric disorders (BHRC) and to test its replicability in the 10-year follow-up (fourth follow-up and phase 3 of the thematic project). Secondly, we intend to investigate the association between age at onset and genomic variants. Material and Methods: 2,500 young people from the BHRC participated in this study, which has been evaluated longitudinally over the last ten years. The genotyping data will come from Illumina's Infinium Global Screening Array and will be analyzed using PLINK software version 2.0 and then a GWAS will be generated using the GENESIS package, using the following as the outcomes of interest: 1) deviations in functionality and 2) the presence of psychiatric diagnoses and replicability during follow-up. The PennCNV tool will be used to generate a list of CNVs and their type of variation (deletion or duplication). The association between genomic variants and age at onset will also be investigated using linear and logistic regressions with the R statistical platform.Expected results and relevance: We hope to identify SNPs with significance for the outcomes of interest and whether they show replicability with the same outcomes at the fourth follow-up. Understanding the genetic basis of mental disorders, as well as outcomes that have a major impact on public health and the economy of a country, can bring great benefits and in the future help to develop intervention measures to improve the outcome of mental disorders.