Analysis of Polygenic Scores for Personality Traits in the Brazilian Population

• Grant number: 25/02190-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• 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

Human personality, by definition, abrange the behaviors observed and performed by human beings. The most widely used scientific methodology is the Five-Factor Model, known as the Big Five (B5). The five factors that encompass personality traits are Neuroticism, Agreeableness, Conscientiousness, Extraversion, and Openness to Experience. B5 traits are multifactorial, with high heritability (45-50%) and a high degree of genetic correlation with psychiatric disorders. For example, neuroticism has a genetic correlation of 70% and 80% with major depression and anxiety, respectively. Personality factors can play an important role in susceptibility and resilience to psychiatric disorder diagnoses. In recent years, the expansion of genetic consortium has enabled the development of a polygenic score (PGS) based on results from Genome-wide association study (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, for example the brazilian population. The objective of this proposal is to compare the prediction of PGS for B5 using different approaches in the Brazilian population. For PGS analysis, the approaches to be used include PRSice, PRS-CS, and DiscoDivas. The data to be analyzed are from the Brazilian High-Risk Cohort Study (BHRCS), which has 14 years of data collected in four phases, with personality trait data for each B5 domain collected in the fourth phase. Based on the results, we aim to assess the prediction accuracy of these approaches in an admixed population and their associations with psychiatric disorders.