Metabolic-dysfunction associated steatotic liver disease-related diseases, cognition and dementia: A two-sample mendelian randomization study

Yao-Shuang Li; Yu-Ge Xia; Yan-Lan Liu; Wei-Ran Jiang; Hui-Na Qiu; Fan Wu; Jing-Bo Li; Jing-Na Lin

doi:10.1371/journal.pone.0297883

Metabolic-dysfunction associated steatotic liver disease-related diseases, cognition and dementia: A two-sample mendelian randomization study

PLoS One. 2024 Feb 29;19(2):e0297883. doi: 10.1371/journal.pone.0297883. eCollection 2024.

Authors

Yao-Shuang Li^{1

2}, Yu-Ge Xia³, Yan-Lan Liu², Wei-Ran Jiang⁴, Hui-Na Qiu², Fan Wu², Jing-Bo Li², Jing-Na Lin²

Affiliations

¹ Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China.
² Department of Endocrinology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China.
³ Geriatric Department, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
⁴ Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, New York, United States of America.

Abstract

Background: The results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia.

Methods: By using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors.

Results: The results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results.

Conclusions: This two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.

Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Alzheimer Disease*
Cognition
Dementia, Vascular*
Humans
Liver Cirrhosis / complications
Liver Cirrhosis / genetics
Mendelian Randomization Analysis
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / genetics

Grants and funding

This work was supported by the Tianjin Science and Technology Committee (J.N.L, Grant Number 18ZXDBSY00120) and the Science and Technology Project of the Tianjin Municipal Health Commission (J.N.L, Grant Number ZD20006). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.