Non-alcoholic fatty liver disease causally affects the brain cortical structure: a Mendelian randomization study

Yu-Kai Lin; Xin-Ran Cai; Jiang-Zhi Chen; Hai-Jie Hong; Kai Tu; Yan-Ling Chen; Qiang Du

doi:10.3389/fnins.2023.1305624

Non-alcoholic fatty liver disease causally affects the brain cortical structure: a Mendelian randomization study

Front Neurosci. 2024 Jan 8:17:1305624. doi: 10.3389/fnins.2023.1305624. eCollection 2023.

Authors

Yu-Kai Lin^{1

2}, Xin-Ran Cai^{1

2}, Jiang-Zhi Chen^{1

2}, Hai-Jie Hong^{1

2}, Kai Tu^{1

2}, Yan-Ling Chen^{1

2}, Qiang Du^{1

2}

Affiliations

¹ Department of Hepatological Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
² Fujian Medical University Cancer Center, Fuzhou, China.

Abstract

Background: Reduced brain volume, impaired cognition, and possibly a range of psychoneurological disorders have been reported in patients with non-alcoholic fatty liver disease (NAFLD); however, no underlying cause has been specified. Here, Mendelian randomization (MR) was employed to determine the causative NAFLD effects on cortical structure.

Methods: We used pooled-level data from FinnGen's published genome-wide association study (GWAS) of NAFLD (1908 cases and 340,591 healthy controls), as well as published GWAS with NAFLD activity score (NAS) and fibrosis stage-associated SNPs as genetic tools, in addition to the Enigma Consortium data from 51,665 patients, were used to assess genetic susceptibility in relation to changes with cortical thickness (TH) and surface area (SA). A main estimate was made by means of inverse variance weighted (IVW), while heterogeneity and pleiotropy were detected using MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier to perform a two-sample MR analysis.

Results: At the global level, NAFLD reduced SA (beta = -586.72 mm², se = 217.73, p = 0.007) and several changes in the cortical structure of the cerebral gyrus were found, with no detectable pleiotropy.

Conclusion: NAFLD causally affects cortical structures, which supports the presence of an intricate liver-brain axis.

Keywords: Mendelian randomization; brain cortical structure; genome-wide association study; liver–brain axis; non-alcoholic fatty liver disease.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Medical “Double High” project of Fujian Medical University Union Hospital (Min Health Medical Administration [2023], No. 76).