Development of a protocol for genome-wide association study to be applied to the investigation of mesial temporal lobe epilepsy in admixed Brazilians

• Grant number: 21/15030-9
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 29, 2022
• End date: August 28, 2023
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Iscia Teresinha Lopes Cendes
• Grantee: Estela Maria Bruxel
• Supervisor: Elizabeth Atkinson
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Baylor College of Medicine, United States
• Associated to the scholarship: 18/03254-7 - Using expression quantitative-trait association studies (eGWAS) to identify loci for mesial temporal lobe epilepsy, BP.PD

Abstract

Epilepsy is a neurological disorder characterized by the permanent predisposition of the brain to generate spontaneous epileptic seizures. Mesial temporal lobe epilepsy (MTLE) is the most frequent form of focal epilepsy in adults, and hippocampal sclerosis (HS) is a common histopathological feature present in patients with MTLE. Genome-wide association studies (GWAS) have been widely used to identify genes involved in complex disorders. Although the number of GWAS in admixed populations has increased over the past few years, there is still a remarkable gap compared with other populations. Population admixture imposes additional challenges for GWAS; however, by applying specific protocols, admixture can also be advantageous in the context of genetic studies. Furthermore, although there are several GWAS studies in epilepsy, the results on MTLE have been disappointing. Thus, this project aims to develop and apply a GWAS protocol suitable to the study of the Brazilian admixed populations and to apply this to a large cohort of patients with MTLE+HS identified in different epilepsy centers in Brazil and Portugal. All patients fulfilled the diagnostic criteria for MTLE+HS proposed by the International League Against Epilepsy. To date, we have enrolled 525 patients and 480 controls. Controls were ethnically matched with patients and were ascertained in the same clinical centers. We used the Affymetrix 6.0 array for SNP genotyping. We will use the software and statistical method Tractor, which was recently developed by the host supervisor, Dr. Elizabeth Atkinson, for association analysis. We expect to develop a tailored analysis pipeline for the Brazilian population, thus addressing important and still unanswered questions regarding population demography, adaptation, and natural selection. The approach described will enable the study of complex traits in individuals with different proportions of admixture found in our country and may be applied to the study of other complex disorders. (AU)