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Causal effects from non-alcoholic fatty liver disease on kidney function: A Mendelian randomization study
Sehoon Park1,2, Soojin Lee3, Yaerim Kim4
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Summary
Nonalcoholic fatty liver disease (NAFLD) causally reduces kidney function, as shown by Mendelian randomization. This finding highlights NAFLD as a risk factor for impaired estimated glomerular filtration rate (eGFR).
Area of Science:
- Nephrology
- Hepatology
- Genetics
Background:
- Observational studies suggest a link between nonalcoholic fatty liver disease (NAFLD) and impaired kidney function.
- The causal relationship between NAFLD and estimated glomerular filtration rate (eGFR) remains unclear.
Purpose of the Study:
- To investigate the causal effect of NAFLD on eGFR using a Mendelian randomization (MR) study.
- To assess the robustness of the association by using genetic instruments and replication datasets.
Main Methods:
- Single-variant and multi-variant MR analyses were performed using genetic variants for NAFLD.
- eGFR data were obtained from the UK Biobank (N=321,405) and CKDGen (N=567,460) datasets.
- Analyses were conducted in subgroups, including a negative control group with low NAFLD probability, to rule out pleiotropy.
Main Results:
- Genetic predisposition to NAFLD was significantly associated with reduced eGFR in the UK Biobank cohort.
- The association remained significant even after adjusting for metabolic disorders.
- Replication analysis using the CKDGen dataset supported the causal effect of NAFLD on reduced eGFR.
Conclusions:
- This MR study provides evidence for a causal relationship between NAFLD and reduced kidney function.
- NAFLD is a potential causal factor for impaired eGFR, emphasizing the need for integrated management of liver and kidney health.
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