Abstract
BACKGROUND: An association has been observed between alcohol and cheese intake and the onset of inflammatory bowel disease (IBD), necessitating further exploration from a genetic structural perspective. METHODS: The present analysis was focused on the intake of alcohol and cheese in conjunction with IBD genome-wide association study (GWAS) data, with the objective of exploring genetic correlations and identifying common loci. Initially, overall genetic correlations were assessed employing two methodologies: linkage disequilibrium score regression (LDSC) and genetic covariance analyzer (GNOVA). Subsequently, local correlations were examined through the SUPERGNOVA method. A genetic overlap analysis between various traits was then conducted based on the statistical theory of conditional/conjunctional false discovery rate (cond/conjFDR). Ultimately, shared loci between the two traits were identified via conjFDR analysis and multi-trait analysis of GWAS (MTAG). RESULTS: Substantial overall correlations were noted at the genome-wide level between alcohol and cheese intake and both IBD and Crohn's disease (CD), whereas the association with ulcerative colitis (UC) was of lesser significance. In the local genetic analysis, chromosome 16 emerged as a key region implicated in the relationship between alcohol and cheese intake and IBD (including both CD and UC). The conjFDR analysis confirmed the genetic overlap between the two diseases. Furthermore, both conjFDR and MTAG analyses identified multiple shared genetic loci, with nine genes (Y_RNA, DENND1B, GCKR, KPNA7, CLN3, SLC39A8, FUT2, ERAP2, and SMAD3) being. CONCLUSION: The present study provides genetic evidence supporting the comorbidity of alcohol and cheese intake with IBD, offering novel insights into potential strategies for the prevention and treatment of IBD through the modulation of alcohol and cheese consumption.