Research Questions
1. Which novel functional genetic variants, especially non-coding SNPs, are significantly associated with pancreatitis risk in the UK Biobank cohort?
2. What are the potential regulatory functions of non-coding risk variants, and how do they influence gene expression or chromatin accessibility in pancreatic tissues?
Research Objectives
1. To perform a comprehensive genome-wide association study (GWAS) using UK Biobank genotype data to identify novel genetic variants associated with pancreatitis risk. The analysis will incorporate stringent quality control, population stratification correction (PCA-based), and covariate adjustment for age, sex, BMI, lifestyle factors and so on.
2. To prioritize candidate functional variants by integrating external pancreatic-specific epigenomic data, including ATAC-seq and ChIP-seq datasets, to define putative cis-regulatory elements (CREs), and by leveraging Hi-C data to link non-coding SNPs to their potential distal target genes.
Scientific Rationale
This research will leverage the unparalleled scale and depth of the UK Biobank’s genomic and clinical resources to construct a high-resolution map of the genetic architecture underlying pancreatitis susceptibility. The GWAS framework enables robust identification of novel loci and refinement of previously reported associations, providing a solid foundation for downstream functional analyses. By integrating genome-wide association signals with epigenomic annotations, transcription factor motif analysis, and 3D chromatin interaction data, this study aims to elucidate how non-coding variants influence gene regulation and contribute to disease risk. Together, these integrative analyses will uncover novel regulatory mechanisms and identify potential therapeutic targets, ultimately advancing our understanding of pancreatitis pathogenesis and informing precision medicine strategies.
