The impact of NAFLD-related indices on brain structure: insights from Mendelian randomization and Bayesian colocalization analysis

Abstract

Abstract: Objective To explore the causal relationship between non-alcoholic fatty liver disease (NAFLD)-related indices and brain structural changes. Methods We selected seven NAFLD-related indices from a genome-wide association study (GWAS) as exposures, and used the data of cerebral cortical thickness and surface area of 51 665 participants from the ENIGMA Consortium as the outcomes. Two-sample Mendelian randomization and Bayesian colocalization were used for analysis. Results The genetically predicted percentage of liver fat was significantly associated with a reduction in the surface area of the parahippocampal region (IVW method: β=-7.871 9 mm², 95% CI: -11.873 2 mm²～-3.870 5 mm², P=1.02 × 10^-4; MR-Egger method: β=-5.180 3 mm², 95% CI: -12.014 4 mm²～1.653 8 mm², P=0.147 1; WM method: β=- 5.501 1 mm², 95% CI: -11.493 9 mm²～0.491 6 mm², P=0.072 0). No evidence of horizontal pleiotropy was detected by the MR-Egger intercept test (Egger intercept = -0.236 7, SE=0.248 6, P=0.348 1), and no heterogeneity was observed by Cochran’s Q test (P=0.845 5), and there was no shared genetic variation between the two phenotypes (PPH4 = 0.016 5). Conclusion There is a significant causal relationship between the percentage of liver fat and brain structure, and this effect seems to be driven by factors other than common genetic variants, which supports the concept of the liver-brain axis.

Key words: Non-alcoholic fatty liver disease, Brain structure, Mendelian randomization, Bayesian colocalization

Chen Chong, Wang Jingying, Zheng Yiyuan, Li Yong. The impact of NAFLD-related indices on brain structure: insights from Mendelian randomization and Bayesian colocalization analysis[J]. Chinese Hepatolgy, 2026, 31(6): 879-885.

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