Genetic underpinnings of inflammatory biomarkers and their interaction with micronutrient status - an integrative evaluation combining Genome Wide Association Studies (GWAS) and a machine learning candidate gene approach

• Grant number: 25/04316-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Marcelo Macedo Rogero
• Grantee: Jean Michel Rocha Sampaio Leite
• Host Institution: Faculdade de Saúde Pública (FSP). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiometabolic diseases (CMD) are among the leading causes of death and loss of quality of life worldwide, resulting in social, economic, and health burdens. The pathophysiology of CMD is closely related to the inflammatory profile, which, along with other cardiometabolic risk factors, can chronically contribute to the onset and progression of various diseases. However, there is a scarcity of: (1) Information on the genetic basis of these markers in admixed populations such as the Brazilian one; (2) Studies assessing the interaction between genetic variants associated with inflammatory markers and micronutrient status in this population, integrating multiple approaches from genetic and data analysis perspectives. Thus, this project proposes a study on the genetic components underlying the inflammatory profile and associated risk factors, using data from the ISA Nutrition 2015 study. The empirical strategy adopted will be based on an integrative data analysis through: (1) Large-scale genome-wide association studies (GWAS) and derivation of polygenic risk scores (PRS) associated with inflammatory biomarkers; (2) Validation of the findings and identification of new genetic variants using machine learning algorithms within the candidate-gene approach; (3) Assessment of the interaction between genetic variants associated with inflammatory markers and other CMD risk factors, such as micronutrient status. The study results will enable the identification of genetic variants with potential biological and clinical relevance, shedding light on their relationship with modulating factors such as micronutrient status, which may play a significant role in the prevention, management, and reduction of CMD impact. (AU)