Unravelling the liver-brain connection: A two-sample Mendelian randomization study investigating the causal relationship between NAFLD and cortical structure

Shitao Jiang; Junwei Zhang; Yaoge Liu; Ting Zhang; Han Zheng; Xinting Sang; Xin Lu; Yiyao Xu

doi:10.1016/j.diabres.2023.110927

Unravelling the liver-brain connection: A two-sample Mendelian randomization study investigating the causal relationship between NAFLD and cortical structure

Diabetes Res Clin Pract. 2023 Oct:204:110927. doi: 10.1016/j.diabres.2023.110927. Epub 2023 Sep 29.

Authors

Shitao Jiang¹, Junwei Zhang¹, Yaoge Liu¹, Ting Zhang¹, Han Zheng¹, Xinting Sang¹, Xin Lu², Yiyao Xu³

Affiliations

¹ Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: luxin@pumch.cn.
³ Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: xuyiyao@pumch.cn.

PMID: 37778665
DOI: 10.1016/j.diabres.2023.110927

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) has been linked to cognitive decline and neuropsychiatric conditions, implying a potential connection between NAFLD and brain health. However, the causal association between NAFLD and cortical changes remains uncertain. This study aimed to examine the causal impact of NAFLD on cortical structures using a two-sample Mendelian randomization (MR) approach.

Methods: Summary data from genome-wide association studies (GWAS) for NAFLD were gathered from large-scale cohorts. Surface area (SA) and cortical thickness (TH) measurements were derived from Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium magnetic resonance imaging (MRI) data of 33,992 participants. Inverse-variance weighted (IVW) served as the primary method. Additional sensitivity analyses, including MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), MR-Egger, and weighted median procedures, were conducted to detect heterogeneity and pleiotropy.

Results: Our MR analysis revealed that NAFLD led to notable alterations in cortical structures, particularly in the pars orbitalis gyrus. Specifically, genetically predicted NAFLD was linked to a decrease in TH (β = -0.008 mm, 95 % CI: -0.013 mm to -0.004 mm, P = 3.00 × 10^-4) within this region. No significant heterogeneity and pleiotropy were identified.

Conclusion: The two-sample MR study supports the existence of a liver-brain axis by demonstrating a causal association between NAFLD and changes in cortical structures. These findings emphasize the potential association between NAFLD and brain health, which could have implications for preventing and treating cognitive deficits and neuropsychiatric conditions in patients with NAFLD.

Keywords: Causal effect; Cortical structure; Mendelian randomization; NAFLD.

Publication types

Meta-Analysis

MeSH terms

Brain / diagnostic imaging
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Non-alcoholic Fatty Liver Disease* / genetics