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已发表论文
从心理到肝脏：基于孟德尔随机化与英国生物样本库验证的焦虑障碍与非酒精性脂肪性肝病因果关系探究
Authors Song H , Dong X , Niu Q , Yu Q, Zhu X , Zhao H, Li C, Lu G, Liu X
Received 12 June 2025
Accepted for publication 26 November 2025
Published 5 December 2025 Volume 2025:18 Pages 7881—7893
DOI https://doi.org/10.2147/JMDH.S546590
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Jagdish Khubchandani
Hui Song,1,* Xiaowu Dong,2,* Qinghui Niu,3 Qian Yu,1 Xiangjia Zhu,4 Hong Zhao,5 Chang Li,6 Guotao Lu,2 Xin Liu7
1Tumor Immunology and Cytotherapy of Medical Research Center, Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 2Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China; 3Department of Liver Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 4Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266000, People’s Republic of China; 6School of Biomedical Sciences, The Chinese University of Hong Kong, 999077, Hong Kong; 7Department of Gastroenterology, Zigong Fourth People’s Hospital, Zigong, 643000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Guotao Lu, Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China, Email gtlu@yzu.edu.cn Xin Liu, Department of Gastroenterology, Zigong Fourth People’s Hospital, Zigong, 643000, People’s Republic of China, Tel +86-18121819266, Email Lxin2020@qdu.edu.cn
Background: Non-alcoholic Fatty Liver Disease (NAFLD) is highly prevalent and increasingly recognized as a multisystem condition with bidirectional links to the brain–liver axis. While most prior work emphasized “liver-to-brain” effects, whether anxiety disorders increase the risk of Non-alcoholic Fatty Liver Disease remains unclear.
Methods: We employed Mendelian randomization (MR) analysis using Genome-wide association study (GWAS) data to investigate whether genetically predicted anxiety disorders play a causal role in NAFLD risk. We then validated our findings using a prospective cohort of 393,229 participants from the UK Biobank, with a median follow-up of 12.6 years.
Results: Our MR analysis provides suggestive evidence for a potential causal effect of genetically predicted anxiety disorders on NAFLD (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.12– 2.67, P = 0.013). This finding was further supported by the UK Biobank prospective study, which demonstrated that baseline anxiety was associated with increased incident NAFLD risk even after adjusting for potential confounding factors (hazard ratio [HR] = 1.630, 95% CI: 1.488– 1.786, P < 0.001). Notably, participants with anxiety exhibited elevated liver fat content at follow-up magnetic resonance imaging, as assessed through follow-up magnetic resonance imaging, irrespective of gender (P < 0.001).
Conclusion: Our study provides converging evidence from genetic and observational data suggesting that anxiety disorders may be associated with an increased risk of NAFLD onset. This relationship necessitates a reconsideration of both NAFLD management and pharmacotherapy for anxiety disorders, advocating for a shift from a specialized clinical focus to a comprehensive community-level strategy for addressing non-communicable diseases (NCDs).
Keywords: anxiety, nonalcoholic fatty liver disease, Mendelian randomization, UK Biobank, prospective study, liver-brain axis
1Tumor Immunology and Cytotherapy of Medical Research Center, Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 2Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China; 3Department of Liver Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 4Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266000, People’s Republic of China; 6School of Biomedical Sciences, The Chinese University of Hong Kong, 999077, Hong Kong; 7Department of Gastroenterology, Zigong Fourth People’s Hospital, Zigong, 643000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Guotao Lu, Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China, Email gtlu@yzu.edu.cn Xin Liu, Department of Gastroenterology, Zigong Fourth People’s Hospital, Zigong, 643000, People’s Republic of China, Tel +86-18121819266, Email Lxin2020@qdu.edu.cn
Background: Non-alcoholic Fatty Liver Disease (NAFLD) is highly prevalent and increasingly recognized as a multisystem condition with bidirectional links to the brain–liver axis. While most prior work emphasized “liver-to-brain” effects, whether anxiety disorders increase the risk of Non-alcoholic Fatty Liver Disease remains unclear.
Methods: We employed Mendelian randomization (MR) analysis using Genome-wide association study (GWAS) data to investigate whether genetically predicted anxiety disorders play a causal role in NAFLD risk. We then validated our findings using a prospective cohort of 393,229 participants from the UK Biobank, with a median follow-up of 12.6 years.
Results: Our MR analysis provides suggestive evidence for a potential causal effect of genetically predicted anxiety disorders on NAFLD (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.12– 2.67, P = 0.013). This finding was further supported by the UK Biobank prospective study, which demonstrated that baseline anxiety was associated with increased incident NAFLD risk even after adjusting for potential confounding factors (hazard ratio [HR] = 1.630, 95% CI: 1.488– 1.786, P < 0.001). Notably, participants with anxiety exhibited elevated liver fat content at follow-up magnetic resonance imaging, as assessed through follow-up magnetic resonance imaging, irrespective of gender (P < 0.001).
Conclusion: Our study provides converging evidence from genetic and observational data suggesting that anxiety disorders may be associated with an increased risk of NAFLD onset. This relationship necessitates a reconsideration of both NAFLD management and pharmacotherapy for anxiety disorders, advocating for a shift from a specialized clinical focus to a comprehensive community-level strategy for addressing non-communicable diseases (NCDs).
Keywords: anxiety, nonalcoholic fatty liver disease, Mendelian randomization, UK Biobank, prospective study, liver-brain axis