(Epi)genetic epidemiology of endocrine disruptors and cardiometabolic traits

Cardiometabolic traits are influenced by both genetic and environmental factors. Among these, endocrine-disrupting chemicals (EDCs) such as bisphenols, parabens and phthalates, prevalent due to global industrialization, are contaminating the environment and food chain, contributing to the increase in obesity and the risk of cardiometabolic diseases like coronary artery disease and type 2 diabetes. The complex relationships between EDCs and cardiometabolic traits, along with the underlying biological mechanisms, are not fully understood. This thesis aimed to investigate the influence of genetic, epigenetic, and inflammatory factors on the association between EDC exposure and cardiometabolic traits. Data from the Lifelines cohort of adults and children from an electronic waste recycling area were analyzed to assess the impacts of genetic variations, DNA methylation, and anti-inflammatory biomarkers on this relationship. The research highlighted that genetic variants related to the excretion of phthalate metabolites, DNA methylation modifications due to environmental exposure, and the role of inflammatory markers in regulating fasting glucose levels are crucial in understanding how EDC exposure impacts cardiometabolic health. This study points to a significant interplay between genetics and environmental factors in influencing cardiometabolic traits. It underscores the need for reducing EDC exposure, particularly among genetically susceptible individuals who metabolize these chemicals ineffectively, and calls for stronger regulations on EDCs, especially in industrially contaminated areas, to mitigate cardiometabolic disease risks.