Cardiometabolic diseases, such as hypertension, diabetes, and cardiovascular disease, pose major global health challenges. These conditions result from a complex interplay of genetic and environmental factors, yet much remains unknown about their genetic basis and how environmental influences modify disease risk.
This thesis of Zekai Chen explores the genetic epidemiology of cardiometabolic outcomes, from understanding heritability to uncovering causal relationships and potential clinical implications. Leveraging large-scale population studies, family-based analyses, and genome-wide association studies, it quantifies the genetic contribution to these diseases and identifies key genetic variants. The research also examines gene-environment interactions, particularly how lifestyle factors such as obesity modify genetic risk for hypertension. To investigate causality, this thesis employs Mendelian Randomization, a method that leverages genetic data to support the inference of cause-and-effect relationships between risk factors and disease outcomes. Additionally, it evaluates drug targets, investigating the effects of lipid-modifying therapies on diabetes risk. By integrating genetic and epidemiological approaches, this work advances our understanding of how genetic and environmental factors jointly shape cardiometabolic health.
These findings offer valuable insights for future research on disease mechanisms and may inform prevention and treatment strategies.
