Whole Transcriptome-wide Analysis Combined With Summary Data-Based Mendelian Randomization Identifies High-Risk Genes...

Cholelithiasis is influenced by various factors, including genetic elements identified in genomewide association studies, but their biological functions are not fully understood.

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 disequilibriums data from the 1000 Genomes Project. Using the Transcriptomewide Association Studies FUSION protocol and summary data-based Mendelian randomization analysis, it investigated the relationship between gene expression and cholelithiasis, using colocalization tests and conditional analyses to explore causality.

The study identified genes associated with cholelithiasis in the liver and whole blood, such as LINC01595, TTC39B, and UGT1A3, with several showing colocalization traits. Notably, RP11-378A13.1 and adenosine deaminase acting on RNA (ADAR) were significantly associated with the disease in both tissues.

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.