Evaluation of the polygenic risk score (PRS) related to the regulation of energy intake associated with body weight and biochemical markers across the population in São Paulo and California with validation of the PRS utilizing the Perturb-seq technology.

• Grant number: 23/17725-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: June 26, 2024
• End date: June 25, 2025
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Marcelo Macedo Rogero
• Grantee: Gabriela de Freitas Laiber Pascoal
• Supervisor: Debora Rodrigues Sobreira
• Host Institution: Faculdade de Saúde Pública (FSP). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of California, Los Angeles (UCLA), United States
• Associated to the scholarship: 23/04689-5 - Polygenic risk score related to energy intake regulation and association with body weight, waist circumference, and diet quality of adolescents, adults, and elderly in the city of Sao Paulo: a population-based study HS-SP, BP.PD

Abstract

Introduction: Effective weight control and body composition rely heavily on regulating energy intake. In this context, it is crucial to study polymorphisms in genes that govern the complex interplay between energy intake and body weight. The polygenic risk score (PRS) has emerged as a robust method that combines the effects of multiple genetic variants to estimate the overall risk associated with complex traits and disorders. Moreover, genome editing technologies, such as Perturb-seq are a crucial research tool for increasing the accuracy and validation of this score. Besides obesity being a polygenic disease, the cultural and ethnic diversity prevalent in Brazil and the USA may contribute to substantial variations in the population's body composition and health determinants. This research internship project aims to assess whether a PRS, incorporating single nucleotide polymorphisms (SNPs) linked to the regulation of energy intake, correlates with body weight and biochemical markers among adults and the elderly in the city of São Paulo and the State of California. Additionally, the study aims to validate the PRS through a comprehensive analysis employing multiple regression models and confirmatory validation utilizing the Perturb-seq genome editing technique. Methods: This project will use the anthropometric and blood markers from two studies: the 2015 Health Survey of São Paulo with a focus in Nutrition (2015 ISA-Nutrition, São Paulo, Brazil) and the Community Health Initiative (The UCLA ATLAS Precision Health Biobank, California, United States of America). A PRS related to energy intake regulation was developed based on 31 SNPs which will be applied to the two available biobanks, with proper normalization based on ancestry for each population, followed by a comparative analysis of the data. The polygenic score will also be validated using CRISPR genome editing analysis. Data will be analyzed using R 4.2.2 version and GraphPad Prism version 9.4 software (San Diego, CA, EUA). Measures of central tendency (mean and median), proportion, and dispersion (95% CI or interquartile range) will be calculated. The normality of the variables will be tested by the Shapiro-Wilk test. Mean comparison tests will be conducted, and linear and multivariate regression models will be built to meet the objectives of the proposal.