This project aims to investigate the shared genetic architecture and epidemiological risk factors underlying major digestive system diseases (such as metabolic dysfunction-associated steatotic liver disease, inflammatory bowel disease, tumor, and other chronic conditions) and their comorbidities with diseases of other organ systems (e.g., cardiovascular, metabolic, and neuropsychiatric disorders).
Research questions include:
1. To what extent do digestive diseases share common genetic variants with other chronic conditions?
2. Are there specific polygenic risk signatures that predict multimorbidity involving the digestive system?
3. What lifestyle, environmental, or demographic factors mediate the observed genetic correlations?
4. Can we identify distinct genetic or epidemiological profiles associated with specific patterns of comorbidity?
Objectives:
1. To perform genome-wide association analyses (GWAS) and cross-trait genetic correlation analyses using UK Biobank genotypic and phenotypic data.
2. To identify pleiotropic loci and shared biological pathways among digestive and non-digestive diseases.
3. To integrate genetic data with epidemiological variables (e.g., diet, smoking, socioeconomic status) using multivariate and machine learning models.
4. To stratify patient subgroups based on shared genetic and risk profiles for targeted preventive strategies.
Scientific rationale:
Digestive diseases often coexist with other chronic conditions, yet the underlying mechanisms remain poorly understood. Shared genetic susceptibility and modifiable risk factors may contribute to these patterns. By analyzing the large-scale, deeply phenotyped data from the UK Biobank cohort, this project will provide novel insights into the biological and environmental mechanisms of multimorbidity, potentially informing future precision prevention and treatment strategies.