非酒精性脂肪肝相关指标对大脑结构的影响:来自孟德尔随机化和贝叶斯共定位分析的见解

肝脏 ›› 2026, Vol. 31 ›› Issue (6): 879-885.

非酒精性脂肪肝相关指标对大脑结构的影响:来自孟德尔随机化和贝叶斯共定位分析的见解

陈冲, 王婧萤, 郑逸远, 李勇

200071 上海上海中医药大学上海市中医医院脾胃病科(陈冲,郑逸远,李勇);
200071 上海上海中医药大学附属第七人民医院,上海中医药大学(陈冲);
210000 南京江苏开放大学健康养生研究所(王婧萤)

收稿日期:2025-05-01 出版日期:2026-06-30 发布日期:2026-07-29
通讯作者: 李勇,Email:liyong@shutcm.edu.cn
基金资助:
上海中医药大学附属第七人民医院人才培养计划(JCR2025-03);上海市浦东新区卫生青年人才(B类);上海自然科学基金项目(3ZR1461200);上海医学创新发展基金会未来计划(WL-YXBS-2022001K);上海市卫生健康委员会(20234Y0142)

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

Chen Chong^1,2, Wang Jingying³, Zheng Yiyuan¹, Li Yong¹

1. Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China;
2. Seventh People′s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China;
3. Institute of Health and Wellness, Jiangsu Open University, Nanjing 210000, China

Received:2025-05-01 Online:2026-06-30 Published:2026-07-29
Contact: LI Yong,Email: liyong@shutcm.edu.cn

摘要/Abstract

摘要： 目的探讨非酒精性脂肪肝相关指标与大脑结构变化之间的因果关系。方法从一项全基因组关联研究中选取了7个与非酒精性脂肪肝相关的指标作为暴露,并利用ENIGMA联盟51 665名参与者的大脑皮层厚度和表面积数据作为结局。利用两样本孟德尔随机化和贝叶斯共定位进行分析。结果遗传预测的肝脏脂肪百分比与海马旁区表面积的减少显著相关(IVW法:β =-7.871 9 mm², 95% CI: -11.873 2 mm²～-3.870 5 mm², P=1.02 × 10^-4;MR-Egger法:β=-5.180 3 mm², 95% CI: -12.014 4 mm²～1.653 8 mm², P=0.147 1;WM法:β= -5.501 1 mm², 95% CI: -11.493 9 mm²～0.491 6 mm², P=0.072 0),未检测到多效性(MR-Egger法:egger_intercept=-0.236 7,se=0.248 6,P=0.348 1)或异质性(Cochran′s test:Q_pval = 0.845 5),且两种表型之间没有共享的遗传变异(PPH4 = 0.016 5)。结论肝脏脂肪百分比与大脑结构之间存在显著因果关系,且这种影响似乎是由共同遗传变异以外的因素驱动的,支持了肝-脑轴的概念。

关键词: 非酒精性脂肪肝, 大脑结构, 孟德尔随机化, 贝叶斯共定位

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

陈冲, 王婧萤, 郑逸远, 李勇. 非酒精性脂肪肝相关指标对大脑结构的影响:来自孟德尔随机化和贝叶斯共定位分析的见解[J]. 肝脏, 2026, 31(6): 879-885.

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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