Background: Cholelithiasis is influenced by various factors, including genetic elements identified in genome-wide association studies (GWAS), but their biological functions are not fully understood.
Methods: Analyzing data from the Finngen database with 37,041 cholelithiasis cases and 330,903 controls, this study combined SNP data from GTEx v8 and linkage disequilibrium data from the 1000 Genomes Project. Using the TWAS FUSION protocol and SMR analysis, it investigated the relationship between gene expression and cholelithiasis, employing colocalization tests and conditional analyses to explore causality.
Results: The study identified genes associated with cholelithiasis in the liver and whole blood, such as LINC01595, TTC39B, UGT1A3, with several showing colocalization traits. Notably, RP11-378A13.1 and ADAR were significantly associated with the disease in both tissues.
Conclusion: This research provides insights into the genetic underpinnings of cholelithiasis, highlighting the significant role of gene expression in its development. It establishes new gene associations and identifies potential genetic markers for the disease.
Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.