Chronic Kidney Disease Does Not Causally Increase the Risk of Cholelithiasis: Evidence from Mendelian Randomization
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i3.4441
Abstract
Background: Chronic kidney disease (CKD) and cholelithiasis are both prevalent conditions that may share metabolic risk factors. However, the causal relationship between CKD and cholelithiasis remains unclear. Methods: A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) summary statistics to assess the potential causal effect of CKD on cholelithiasis. Genetic variants significantly associated with CKD were selected as instrumental variables. The inverse variance weighted (IVW) method served as the primary analysis, supplemented by MR-Egger and weighted median approaches. Sensitivity analyses included assessments of pleiotropy, heterogeneity, and leave-one-out stability. Results: MR analysis showed no significant causal effect of CKD on cholelithiasis (IVW OR = 0.948, 95% CI: 0.835–1.077, P = 0.414). Sensitivity analyses found no evidence of pleiotropy or heterogeneity, and leave-one-out analysis supported the robustness of the findings. Conclusion: This MR analysis found no evidence supporting a causal effect of CKD on the risk of developing cholelithiasis. The results suggest that genetic liability to CKD does not significantly increase the likelihood of gallstone formation. Further investigations across diverse populations are warranted to confirm these findings and to explore potential shared pathways underlying both conditions.
Keywords
Genetic variants; Chronic kidney disease; Cholelithiasis; Risk factors
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[5]Wang HH, Portincasa P, Liu M, Wang DQ. Genetic Analysis of ABCB4 Mutations and Variants Related to the Pathogenesis and Pathophysiology of Low Phospholipid-Associated Cholelithiasis. Genes (Basel). 2022;13(6):1047. Published 2022 Jun 11. doi:10.3390/genes13061047
[6]Ye Z, Xie J, Ni X, et al. Physical activity and risk of cholelithiasis: a narrative review. Front Med (Lausanne). 2024;11:1485097. Published 2024 Dec 16. doi:10.3389/fmed.2024.1485097
[7]Petrola Chacón CG, Vilallonga R, González López Ó, et al. Analysis of the Management of Cholelithiasis in Bariatric Surgery Patients: a Single-Center Experience. Obes Surg. 2022;32(3):704-711. doi:10.1007/s11695-021-05883-z
[8]Karahan D, Şahin İ. Evaluation of hepatosteatosis and gallstone disease in patients with chronic kidney disease. Hemodial Int. 2024;28(3):343-350. doi:10.1111/hdi.13151
[9]Sanderson E, Glymour MM, Holmes MV, et al. Mendelian randomization. Nat Rev Methods Primers. 2022;2:6. doi:10.1038/s43586-021-00092-5
[10]Verduijn M, Siegerink B, Jager KJ, Zoccali C, Dekker FW. Mendelian randomization: use of genetics to enable causal inference in observational studies. Nephrol Dial Transplant. 2010;25(5):1394-1398. doi:10.1093/ndt/gfq098
[11]de Leeuw C, Savage J, Bucur IG, Heskes T, Posthuma D. Understanding the assumptions underlying Mendelian randomization. Eur J Hum Genet. 2022;30(6):653-660. doi:10.1038/s41431-022-01038-5
[12]Xue H, Liu S, Zeng L, Fan W. Causal effect of systemic lupus erythematosus on psychiatric disorders: A two-sample Mendelian randomization study. J Affect Disord. 2024;347:422-428. doi:10.1016/j.jad.2023.11.033
[13]Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658-665. doi:10.1002/gepi.21758
[14]Boehm FJ, Zhou X. Statistical methods for Mendelian randomization in genome-wide association studies: A review. Comput Struct Biotechnol J. 2022;20:2338-2351. Published 2022 May 14. doi:10.1016/j.csbj.2022.05.015
[15]Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: A review. Res Synth Methods. 2019;10(4):486-496. doi:10.1002/jrsm.1346
[16]Nguyen K, Mitchell BD. A Guide to Understanding Mendelian Randomization Studies. Arthritis Care Res (Hoboken). 2024;76(11):1451-1460. doi:10.1002/acr.25400
[17]Qing X, Jiang J, Yuan C, Xie K, Wang K. Temporal trends in prevalence and disability of chronic kidney disease caused by specific etiologies: an analysis of the Global Burden of Disease Study 2019. J Nephrol. 2024;37(3):723-737. doi:10.1007/s40620-024-01914-x
[18]Krishnan A, Teixeira-Pinto A, Lim WH, et al. Health-Related Quality of Life in People Across the Spectrum of CKD. Kidney Int Rep. 2020;5(12):2264-2274. Published 2020 Oct 3. doi:10.1016/j.ekir.2020.09.028
[19]Dan WY, Yang YS, Peng LH, Sun G, Wang ZK. Gastrointestinal microbiome and cholelithiasis: Current status and perspectives. World J Gastroenterol. 2023;29(10):1589-1601. doi:10.3748/wjg.v29.i10.1589
[20]Koller T, Kollerova J, Hlavaty T, Huorka M, Payer J. Cholelithiasis and markers of nonalcoholic fatty liver disease in patients with metabolic risk factors. Scand J Gastroenterol. 2012;47(2):197-203. doi:10.3109/00365521.2011.643481
[21]Talha A, Abdelbaki T, Farouk A, Hasouna E, Azzam E, Shehata G. Cholelithiasis after bariatric surgery, incidence, and prophylaxis: randomized controlled trial. Surg Endosc. 2020;34(12):5331-5337. doi:10.1007/s00464-019-07323-7
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