Application of Polygenic Score for Eating Disorders in a Admixed Population

• Grant number: 24/04224-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2024
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marcos Leite Santoro
• Grantee: Diego Ortunes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 23/05560-6 - Genetic and epigenetic approaches as predictive models in mental disorders, AP.JP

Abstract

Psychiatric disorders affect around 12% of the world's population and are among the leading causes of Disability-adjusted life years. Eating disorders (ED) and obsessive-compulsive disorder (OCD) are examples of psychiatric disorders that show a high degree of correlation and genetic overlap. The high heritability of Anorexia Nervosa, a major type of ED, and OCD suggests that the genome contains a wealth of information that has the potential to be used as genetic risk markers for these disorders. However, the polygenic nature of these diseases, combined with the influence of environmental factors, complicates the exploration of this information. In recent years, the expansion of psychiatric genomics consortium has allowed the creation of a polygenic score (PGS) based on results from Genome-Wide Association Studies (GWAS). With the increasing availability of GWAS data, new methods for constructing PGS have emerged. One limitation of PGS is a better prediction for the population of European ancestry, due to the majority of GWAS in this populations, making it challenging to apply to non-European and admixed samples, such as the Brazilian population. The overall objective of this proposal is to compare the prediction of PGS for ED and OCD using different approaches in a admixed population. For PGS analysis, the approaches used will be PRS-CS and GAUDI. The data to be analyzed are from patients in the Brazilian High Risk Cohort Study (BHRCS), which has 13 years of data collected in three phases, cases will be considered those diagnosed with ED or OCD in any segment of the study, along with the most recent GWAS for each phenotype. The expectation is to determine the prediction and accuracy of these approaches in the admixed population based on the results.