I. Research Questions and Aims
* Main Aim
o Evaluate the associations of environmental and genetic factors with common age-related diseases.
* Specific Objectives
o Integrate environmental exposure factors assessed by the UKB with other exposures (e.g., air pollution, green space, extreme temperatures, genetic predisposition).
o Investigate the associations between these exposures and common age-related diseases such as type 2 diabetes mellitus, chronic kidney disease, and metabolic syndrome.
o Explore potential mediators and predictors within these relationships.
o Incorporate omics data (proteomics, NMR-based metabolomics) and clinical/laboratory indicators (blood pressure, blood lipids, telomere length).
II. Background and Scientific Rationale
* Significance of Age-related Diseases
o Aging and related diseases impose significant socioeconomic burdens and affect patients’ quality of life.
* Role of Environmental Factors
o Air pollution plays a crucial role in the occurrence and progression of age-related diseases.
o Interacts with factors like green space area and temperature conditions, leading to combined effects.
o Current population studies are insufficient due to limitations in design and participant numbers.
* Advancements in Genetic Research
o Genome-wide association studies have identified multiple genetic loci related to type 2 diabetes, chronic kidney disease, and metabolic diseases.
o Polygenic risk scores effectively measure the cumulative effects of multiple risk-associated variants.
* Proposed Research Approach
o Analyze UKB data and use external cohorts for validation.
o Systematically assess interactions between multiple environmental exposure factors and genetic factors.
o Investigate their combined effects on age-related diseases.
o Investigate molecular mechanisms underlying these processes.
