Liu Xuxu, Wang Heming, Xie Zhihong, Li Lianghao, He Yuanhang, Meng Ziang, Li Jiachen, Yu Jingjing, Du Zhiwei, Zheng Yi, Liu Tianming, Hao Chenjun, Xue Dongbo, Wang Liyi, Gao Enjun
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China .
Clin Transl Gastroenterol. 2025 May 1;16(5):e00800. doi: 10.14309/ctg.0000000000000800.
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.
胆结石受多种因素影响，包括全基因组关联研究中确定的遗传因素，但其生物学功能尚未完全了解。
本研究分析了来自芬兰基因数据库的37041例胆结石病例和330903例对照的数据，结合了GTEx v8的单核苷酸多态性（SNP）数据和千人基因组计划的连锁不平衡数据。使用全转录组关联研究融合协议和基于汇总数据的孟德尔随机化分析，研究基因表达与胆结石之间的关系，并使用共定位测试和条件分析来探索因果关系。
该研究在肝脏和全血中鉴定出与胆结石相关的基因，如LINC01595、TTC39B和UGT1A3，其中一些显示出共定位特征。值得注意的是，RP11-378A13.1和作用于RNA的腺苷脱氨酶（ADAR）在两种组织中均与该疾病显著相关。
本研究为胆结石的遗传基础提供了见解，强调了基因表达在其发展中的重要作用。它建立了新的基因关联，并确定了该疾病的潜在遗传标记。
