From Mind to Liver: Exploring the Causal Relationship Between Anxiety Disorders and Non-Alcoholic Fatty Liver Disease Through Mendelian Randomization and UK Biobank Validation
Bibliographic record
Abstract
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 workCorrespondence: 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.cnBackground: 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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.048 | 0.123 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".