Observational, causal relationship and shared genetic basis between cholelithiasis and gastroesophageal reflux disease: evidence from a cohort study and comprehensive genetic analysis

被引：0

作者：

Lyu, Yanlin ^{[1
,2
,3
]}

Tong, Shuangshuang ^{[1
,3
]}

Huang, Wentao ^{[1
,2
]}

Ma, Yuying ^{[1
,2
]}

Zeng, Ruijie ^{[1
,3
]}

Jiang, Rui ^{[1
,4
]}

Luo, Ruibang ^{[5
]}

Leung, Felix W. ^{[6
,7
]}

Lian, Qizhou ^{[8
,9
,10
]}

Sha, Weihong ^{[1
,2
,3
,4
]}

Chen, Hao ^{[1
,2
,3
,4
]}

机构：

[1] Southern Med Univ, Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Gastroenterol, Guangzhou 510080, Peoples R China

[2] Southern Med Univ, Sch Clin Med 2, Guangzhou 510515, Peoples R China

[3] Shantou Univ, Med Coll, Shantou 515041, Peoples R China

[4] South China Univ Technol, Sch Med, Guangzhou 510006, Peoples R China

[5] Univ Hong Kong, Dept Comp Sci, Hong Kong 999077, Peoples R China

[6] VA Greater Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA 91343 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[8] Chinese Acad Sci, Shenzhen Inst Adv Technol, Fac Synthet Biol, Shenzhen 518055, Peoples R China

[9] Guangzhou Med Univ, Guangzhou Inst Eugenics & Perinatol, Guangzhou Women & Childrens Med Ctr, Cord Blood Bank, Guangzhou 510623, Peoples R China

[10] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong 999077, Peoples R China

来源：

GIGASCIENCE | 2025年 / 14卷

基金：

中国国家自然科学基金;

关键词：

cholelithiasis; gastroesophageal reflux disease; cohort study; Mendelian randomization; genetic analyses; causal association; shared genetic basis; MENDELIAN RANDOMIZATION; CHOLESTEROL; 7-ALPHA-HYDROXYLASE; IMPAIRED GALLBLADDER; GALLSTONE DISEASE; BILE-ACID; ASSOCIATION; STATISTICS; MOTILITY; POLYMORPHISMS; METAANALYSIS;

D O I：

10.1093/gigascience/giaf023

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Objective Cholelithiasis and gastroesophageal reflux disease (GERD) contribute to significant health concerns. We aimed to investigate the potential observational, causal, and genetic relationships between cholelithiasis and GERD.Design The observational correlations were assessed based on the prospective cohort study from UK Biobank. Then, by leveraging the genome-wide summary statistics of cholelithiasis (N = 334,277) and GERD (N = 332,601), the bidirectional causal associations were evaluated using Mendelian randomization (MR) analysis. Subsequently, a series of genetic analyses was used to assess the genetic correlation, shared loci, and genes between cholelithiasis and GERD.Results The prospective cohort analyses revealed a significantly increased risk of GERD in individuals with cholelithiasis (hazard ratio [HR] = 1.99; 95% confidence interval [CI], 1.89-2.10) and a higher risk of cholelithiasis among patients with GERD (HR = 2.30; 95% CI, 2.18-2.44). The MR study indicated the causal effect of genetic liability to cholelithiasis on the incidence of GERD (odds ratio [OR] = 1.08; 95% CI, 1.05-1.11) and the causal effect of genetic predicted GERD on cholelithiasis (OR = 1.15; 95% CI, 1.02-1.31). In addition, cholelithiasis and GERD exhibited a strong genetic association. Cross-trait meta-analyses identified 5 novel independent loci shared between cholelithiasis and GERD. Three shared genes, including SUN2, CBY1, and JOSD1, were further identified as novel risk genes.Conclusion The elucidation of the shared genetic basis underlying the phenotypic relationship of these 2 complex phenotypes offers new insights into the intrinsic linkage between cholelithiasis and GERD, providing a novel research direction for future therapeutic strategy and risk prediction.

引用

页数：14

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