Atherosclerotic cardiovascular disease (ASCVD) and non-alcoholic fatty liver disease (NAFLD) are closely interrelated conditions that share common pathophysiological pathways including dyslipidemia, insulin resistance, and chronic inflammation. Despite their frequent co-occurrence and substantial global health burden, the molecular mechanisms underlying their relationship remain incompletely understood. This study aims to comprehensively characterize the multi-omics signatures linking ASCVD and NAFLD progression. Using UK Biobank’s extensive multimodal data, we will first identify shared genetic variants associated with both conditions through genome-wide association studies, focusing on lipid metabolism, inflammatory response, and fibrotic pathways. Second, we will analyze plasma metabolomic and proteomic profiles to elucidate circulating biomarkers that reflect the cross-talk between hepatic steatosis and vascular inflammation, including metabolites related to lipid partitioning, oxidative stress, and inflammatory mediators. Third, we will integrate quantitative imaging features from cardiac MRI, carotid ultrasound, and abdominal imaging with molecular data to develop predictive models for disease progression and cardiovascular outcomes in patients with NAFLD. Our integrated approach will bridge molecular mechanisms with clinical phenotypes, ultimately aiming to improve risk stratification and enable targeted interventions for this high-risk population.
