Dataset Information

Sleep duration and age-related macular degeneration: a cross-sectional and Mendelian randomization study.

ABSTRACT:

Purpose

To investigate the association between sleep duration and age-related macular degeneration (AMD).

Design

Cross-sectional study, bidirectional two-sample Mendelian randomization (MR). For cross-sectional analysis, we used survey data of 5,481 participants aged ≥40 years from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES). For MR analysis, we used sleep- and AMD-associated genome-wide association studies (GWAS) data involving large populations.

Methods

The association between sleep duration and AMD was assessed using logistic regression models. For MR analysis, the primary approach for MR analysis was the inverse-variance weighted (IVW) method.

Results

In cross-sectional analysis, after adjusting for multiple covariates, short sleep duration (SSD) was found to be associated with increased risk of early AMD [odds ratio (OR) = 1.364, P = 0.036). MR analysis supported the results of cross-sectional analysis: SSD increases the risk of early AMD (β = 0.102, IVW-P = 0.003).

Conclusion

Our findings provide the evidence supporting the association between sleep deficiency and higher risk of AMD. Further studies are required to confirm our findings and elucidate the mechanisms underlying this association.

SUBMITTER: Lei S

PROVIDER: S-EPMC10477604 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Sleep duration and age-related macular degeneration: a cross-sectional and Mendelian randomization study.

Lei Shizhen S Liu Zhouyang Z Li Haihui H

Frontiers in aging neuroscience 20230822

<h4>Purpose</h4>To investigate the association between sleep duration and age-related macular degeneration (AMD).<h4>Design</h4>Cross-sectional study, bidirectional two-sample Mendelian randomization (MR). For cross-sectional analysis, we used survey data of 5,481 participants aged ≥40 years from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES). For MR analysis, we used sleep- and AMD-associated genome-wide association studies (GWAS) data involving large populations.<h4 ...[more]

PMID: 37674785

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Project description:BackgroundCurrently, effective therapeutic drugs for age-related macular degeneration (AMD) are urgently needed, and it is crucial to explore new treatment targets. The proteome is indispensable for exploring disease targets, so we conducted a Mendelian randomization (MR) of the proteome to identify new targets for AMD and its related subtypes.MethodsThe plasma protein level data used in this study were obtained from two large-scale studies of protein quantitative trait loci (pQTL), comprising 35,559 and 54,219 samples, respectively. The expression quantitative trait loci (eQTL) data were sourced from eQTLGen and GTEx Version 8. The discovery set for AMD data and subtypes was derived from the FinnGen study, consisting of 9,721 AMD cases and 381,339 controls, 5,239 wet AMD cases and 273,920 controls, and 6,651 dry AMD cases and 272,504 controls. The replication set for AMD data was obtained from the study by Winkler TW et al., comprising 14,034 cases and 91,234 controls. Summary Mendelian randomization (SMR) analysis was employed to assess the association between QTL data and AMD and its subtypes, while colocalization analysis was performed to determine whether they share causal variants. Additionally, chemical exploration and molecular docking were utilized to validate potential drugs targeting the identified proteins.ResultsSMR and colocalization analysis jointly identified risk-associated proteins for AMD and its subtypes, including 5 proteins (WARS1, BRD2, IL20RB, TGFB1, TNFRSF10A) associated with AMD, 2 proteins (WARS1, IL20RB) associated with Dry-AMD, and 9 proteins (COL10A1, WARS1, VTN, SDF2, LBP, CD226, TGFB1, TNFRSF10A, CSF2) associated with Wet-AMD. The results revealed potential therapeutic chemicals, and molecular docking indicated a good binding between the chemicals and protein structures.ConclusionProteome-wide MR have identified risk-associated proteins for AMD and its subtypes, suggesting that these proteins may serve as potential therapeutic targets worthy of further clinical investigation.

Project description:Using genome-wide association study data from European populations, this research clarifies the causal relationship between plasma metabolites and age-related macular degeneration (AMD) and employs Metabo Analyst 5.0 for enrichment analysis to investigate their metabolic pathways. Employing Mendelian randomization analysis, this study leveraged single nucleotide polymorphisms significantly associated with plasma metabolites as instrumental variables. This approach established a causal link between metabolites and AMD. Analytical methods such as inverse-variance weighted, Mendelian randomization-Egger, and weighted median were applied to validate causality. Mendelian Randomization Pleiotropy Residual Sum and Outlier was utilized for outlier detection and correction, and Cochran's Q test was conducted to assess heterogeneity. To delve deeper into the metabolic characteristics of AMD, metabolic enrichment analysis was performed using Metabo Analyst 5.0. These combined methods provided a robust framework for elucidating the metabolic underpinnings of AMD. The 2-sample MR analysis, after meticulous screening, identified causal relationships between 88 metabolites and AMD. Of these, 16 metabolites showed a significant causal association. Following false discovery rate correction, 3 metabolites remained significantly associated, with androstenediol (3 beta, 17 beta) disulfate (2) exhibiting the most potent protective effect against AMD. Further exploration using Metabo Analyst 5.0 highlighted 4 metabolic pathways potentially implicated in AMD pathogenesis. This pioneering MR study has unraveled the causal connections between plasma metabolites and AMD. It identified several metabolites with a causal impact on AMD, with 3 maintaining significance after FDR correction. These insights offer robust causal evidence for future clinical applications and underscore the potential of these metabolites as clinical biomarkers in AMD screening, treatment, and prevention strategies.

Project description:PurposeRecently, the association between gut microbiota and age-related macular degeneration (AMD) through the gut-retina axis has attracted great interest. However, the causal relationship between them has not been elucidated. Using publicly available genome-wide association study summary statistics, we conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiota and the occurrence of AMD.MethodsThe study used a variety of quality control techniques to select instrumental single nucleotide polymorphisms (SNPs) with strong exposure associations. We used a set of SNPs as instrumental variable that were below the genome-wide statistical significance threshold (5 × 10-8). Additionally, a separate group of SNPs below the locus-wide significance level (1 × 10-5) were selected as instrumental variables to ensure a comprehensive conclusion. Inverse variance-weighted (IVW) analysis was the primary technique we used to examine causality in order to confirm the validity of our findings. The MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis were used to evaluate the horizontal pleiotropy, heterogeneities, and stability of the genetic variants.ResultsIVW results showed that genus Anaerotruncus (P = 5.00 × 10-3), genus Candidatus Soleaferrea (P = 1.83 × 10-2), and genus unknown id.2071 (P = 3.12 × 10-2) were protective factors for AMD. The Eubacterium oxidoreducens group (P = 3.17 × 10-2), genus Faecalibacterium (P = 2.67 × 10-2), and genus Ruminococcaceae UCG-011 (P = 4.04 × 10-2) were risk factors of AMD. No gut microbiota (GM) taxa were found to be causally related to AMD at the phylum, class, order, and family levels (P > 0.05). The robustness of MR results were confirmed by heterogeneity and pleiotropy analysis. (P > 0.05). We also performed a bidirectional analysis, which showed that genus Anaerotruncus, genus Candidatus Soleaferrea, genus unknown id.2071 and the Eubacterium oxidoreducens group had an interaction with AMD, whereas genus Faecalibacterium showed only a unilateral unfavorable effect on AMD.ConclusionsWe confirmed a causal relationship between AMD and GM taxa, including the Eubacterium oxidoreducens group, Faecalibacterium, Ruminococcaceae UCG-011, Anaerotruncus, and Candidatus Soleaferrea. These strains have the potential to serve as new biomarkers, offering valuable insights into the treatment and prevention of AMD.

Dataset Information

Sleep duration and age-related macular degeneration: a cross-sectional and Mendelian randomization study.

Purpose

Design

Methods

Results

Conclusion

Publications

Sleep duration and age-related macular degeneration: a cross-sectional and Mendelian randomization study.

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