Dataset Information

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD.

ABSTRACT:

Background

Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis.

Methods

Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy.

Results

Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes.

Conclusion

This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.

SUBMITTER: Mao Z

PROVIDER: S-EPMC10885469 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD.

Mao Zun Z Gao Zhi-Xiang ZX Ji Tong T Huan Sheng S Yin Guo-Ping GP Chen Long L

Lipids in health and disease 20240223 1

<h4>Background</h4>Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis.<h4>Methods</h4>Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participan ...[more]

PMID: 38395962

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Dataset Information

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD.

Background

Methods

Results

Conclusion

Publications

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD.

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