Scientific Rationale: AF is the most common sustained arrhythmia, and emerging evidence suggests a rising prevalence in patients with metabolic syndromes, including MASH (formerly known as NASH). MASH is a progressive liver disease characterized by steatosis, inflammation, and fibrosis, frequently coexisting with obesity, insulin resistance, and systemic inflammation-factors also implicated in atrial remodeling and AF pathogenesis. However, the precise mechanistic and epidemiologic links between MASH and AF remain underexplored. Leveraging the extensive phenotypic, imaging, and genetic data of the UK Biobank, this project aims to uncover shared pathogenic mechanisms and identify predictive markers, thereby informing risk stratification and potential prevention strategies.
Research Questions:
1. Is there a causal association between MASH/Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) and increased risk of AF?
2. What clinical and molecular biomarkers mediate this association?
3. Do shared genetic predispositions or systemic metabolic-inflammatory pathways underpin the co-occurrence of MASH and AF?
Objectives:
* To evaluate the prevalence and incidence of AF in individuals with MASH or MAFLD using imaging, biochemical, and diagnostic code data from UK Biobank.
* To identify shared cardiometabolic and inflammatory risk profiles associated with both conditions.
* To investigate genetic variants linked to MASH and AF through genome-wide association analyses and Mendelian randomization.
* To examine liver stiffness, fat content, and systemic inflammatory biomarkers as predictors of AF onset in longitudinal follow-up.
