Genome-wide association study (GWAS) for the identification of genetic variants related to the primary open-angle glaucoma development in a Brazilian population sample

• Grant number: 23/16456-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2024
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mônica Barbosa de Melo
• Grantee: Thiago Adalton Rosa Rodrigues
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Primary open-angle glaucoma (POAG) is the most prevalent cause of irreversible blindness worldwide, characterized as an asymptomatic, neurodegenerative, and multifactorial etiology disease. Its primary feature is the progressive loss of retinal ganglion cells (RGCs) leading to subsequent progressive damage to the optic disc. Interactions among systemic, environmental, and genetic factors, along with various risk factors including ethnicity, familial aggregation, and elevated intraocular pressure, contribute to the pathophysiology of POAG. Therefore, the identification of genetic variants represents a crucial step in precision medicine. To date, 127 single nucleotide variants related to the condition have been identified through Genome-Wide Association Studies (GWAS) in predominantly homogeneous populations, including Caucasian and Asian ethnicities. However, the diversity of findings remains limited, as investigations in admixed cohorts, such as the Brazilian population, are rare despite Latin America representing the second-highest global prevalence. In this study, we propose to conduct a GWAS of POAG in a sample of the Brazilian population, representative of different regions of the country. Two cohorts will be evaluated: the discovery cohort, comprising 2000 cases and 2000 controls, and the validation cohort, comprising 1000 cases and 1000 controls from the same regions. The analysis will be performed using the Infinium Global Screening Array-24 MD v3.0 microarray (Illumina, Inc., San Diego, CA, USA). In addition to identifying risk variants for POAG in this population, we aim to use the generated data to assess the applicability of models developed for European and multiethnic populations. This pioneering study in the Brazilian population with POAG aims to deepen our understanding of the genetic profile of a population with unique ethnic composition, hoping to contribute to the global knowledge of this condition and facilitate the advancement of precision medicine.