A two-sample mendelian randomization analysis excludes causal relationships between non-alcoholic fatty liver disease and kidney stones

Xintao Li; Yongpeng Xie; Lu Tang; Di Li; Jun Wang; Haibo Sheng; Kaikai Chen; Shuwei Xiao; Jianye Li; Minghui Yang

doi:10.3389/fendo.2023.1343367

A two-sample mendelian randomization analysis excludes causal relationships between non-alcoholic fatty liver disease and kidney stones

Front Endocrinol (Lausanne). 2024 Jan 10:14:1343367. doi: 10.3389/fendo.2023.1343367. eCollection 2023.

Authors

Xintao Li^#^{1

2

3}, Yongpeng Xie^#⁴, Lu Tang^#², Di Li³, Jun Wang³, Haibo Sheng³, Kaikai Chen³, Shuwei Xiao³, Jianye Li³, Minghui Yang¹

Affiliations

¹ Department of Traditional Chinese Medicine, The Sixth Medical Centre, Chinese People's Liberation Army General Hospital, Beijing, China.
² Department of Urology, The Third Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
³ Department of Urology, Air Force Medical Center, Air Force Medical University, Beijing, China.
⁴ Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

^# Contributed equally.

Abstract

Objectives: Non-alcoholic fatty liver disease (NAFLD) has been linked to an increased risk of kidney stones in prior observational studies, However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between NAFLD and kidney stones using two-sample Mendelian randomization (MR).

Methods: Genetic instruments were used as proxies for NAFLD. Summary-level data for the associations of exposure-associated SNPs with kidney stones were obtained from the UK Biobank study (6536 cases and 388,508 controls) and the FinnGen consortium (9713 cases and 366,693 non-cases). MR methods were conducted, including inverse variance weighted method (IVW), MR-Egger, weighted median, and MR-PRESSO. MR-Egger Regression Intercept and Cochran's Q test were used to assess the directional pleiotropy and heterogeneity.

Results: cALT-associated NAFLD did not exhibit an association with kidney stones in the Inverse variance weighted (IVW) methods, in both the FinnGen consortium (OR: 1.02, 95%CI: 0.94-1.11, p = 0.632) and the UKBB study (OR: 1.000, 95%CI: 0.998-1.002, p = 0.852). The results were consistent in European ancestry (FinnGen OR: 1.05, 95%CI: 0.98-1.14, p = 0.144, UKBB OR: 1.000, 95%CI: 0.998-1.002, p = 0.859). IVW MR analysis also did not reveal a significant causal relationship between NAFLD and the risk of kidney stone for the other three NAFLD-related traits, including imaging-based, biopsy-confirmed NAFLD, and more stringent biopsy-confirmed NAFLD. The results remained consistent and robust in the sensitivity analysis.

Conclusions: The MR study did not provide sufficient evidence to support the causal associations of NAFLD with kidney stones.

Keywords: Mendelian randomization; NAFLD; causality; genome wide association study; kidney stone.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Biopsy
Causality
Humans
Kidney Calculi* / etiology
Kidney Calculi* / genetics
Mendelian Randomization Analysis
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / epidemiology
Non-alcoholic Fatty Liver Disease* / genetics

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No. 81900718), Outstanding Young Talent Program of Air Force Medical Center (No.2022YXQN27) and Military Logistics Research Project (grant number: 21QNPY081).