Exploring the impact of diet, sleep, and metabolomic pathways on Glaucoma subtypes: insights from Mendelian randomization and cross-sectional analyses

Abstract

Background: Glaucoma is a leading cause of irreversible blindness, influenced by systemic and lifestyle factors. This study investigates the causal relationships between dietary habits, sleep traits, amino acids, metabolites, and inflammatory factors with glaucoma subtypes using Mendelian randomization (MR) and validates findings through cross-sectional analysis.

Methods: MR analysis assessed the causal effects of 226 dietary factors, 11 sleep traits, 20 amino acids, 1400 metabolites, and 91 inflammatory factors on five glaucoma subtypes (NTG, POAG, PACG, NVG, XFG). Mediation MR analysis explored the role of amino acids and inflammatory factors in these relationships. Validation was conducted using NHANES cross-sectional data.

Results: High-fat, high-calorie diets increased glaucoma risk, while antioxidant-rich foods and better sleep quality reduced it. Key mediators included proline, tyrosine, IL-1 A, and PDL1. NHANES data confirmed lower intake of vitamins A and C, higher water consumption among glaucoma patients, and significant sleep-related associations.

Conclusion: Our findings highlight the role of balanced diets and optimized sleep patterns in glaucoma prevention and management. This study provides evidence for targeted lifestyle interventions focusing on metabolic and inflammatory pathways to mitigate glaucoma risk.

Keywords: Amino acids; Dietary habits; Glaucoma; Inflammatory factors; Lifestyle interventions; Mendelian randomization; Metabolomics; NHANES; Neuroprotection.; Sleep traits.

Fig. 1

Study design

Fig. 2

A: The causal effects between Dietary Intake and NTG. B: The causal effects between Dietary Intake and PACG. C: The causal effects between Dietary Intake and POAG. D: The causal effects between Dietary Intake and NVG. E: The causal effects between Dietary Intake and XFG

Fig. 3

The causal effects between Sleep and Glaucoma

Fig. 4

A: The causal effects between amino acids and glaucoma. B: The enrichment of significant metabolites in POAG. C: The enrichment of significant metabolites in PACG. D: The Enrichment of significant metabolites in NTG

Fig. 5

The causal effects between inflammatory factors and glaucoma subtypes. Abbreviations: IL-1 A (interleukin-1α); PDL1 (programmed death-ligand 1); 2B4 (CD244, also known as SLAMF4); CX3CL1 (C-X3-C motif chemokine ligand 1, i.e., fractalkine); CCL28 (C-C motif chemokine ligand 28); CXCL11 (C-X-C motif chemokine ligand 11); CCL19 (C-C motif chemokine ligand 19); CDCP1 (CUB domain-containing protein 1); CSF1 (colony-stimulating factor 1); S100-A12 (S100 calcium-binding protein A12); IL-10 (interleukin-10); MMP-10 (matrix metalloproteinase-10); TWEAK (TNF-related weak inducer of apoptosis, TNFSF12); uPA (urokinase plasminogen activator); eIF4E-BP1 (eukaryotic initiation factor 4E binding protein 1); IL-6 (interleukin-6); SCF (stem cell factor, also known as KIT ligand); FGF19 (fibroblast growth factor 19); TNFRSF9 (tumor necrosis factor receptor superfamily member 9, CD137); IL-24 (interleukin-24); IL-18 (interleukin-18); IL-10RA (interleukin-10 receptor subunit alpha); CXCL1 (C-X-C motif chemokine ligand 1); MMP-1 (matrix metalloproteinase-1); CXCL9 (C-X-C motif chemokine ligand 9); TGF-A (transforming growth factor alpha); MCP-3 (monocyte chemoattractant protein-3, CCL7); IL-17 C (interleukin-17 C); MCP-2 (monocyte chemoattractant protein-2, CCL8); FGF21 (fibroblast growth factor 21)