Sleep, Pain, and Neurodegeneration: A Mendelian Randomization Study

Grover, Sandeep; Sharma, Manu

doi:10.3389/fneur.2022.765321

Cited by 11 publications

(7 citation statements)

References 51 publications

(67 reference statements)

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“…Following reason can explain why our study found a significant association between sleep duration and AMD but the previous MR study failed. First, the sample size was five-fold increased in this study (150,642) than others (33,976) ( Grover et al, 2022 ). Second, it’s worth noting that the sleep duration only have minimal effect on AMD (OR = 0.983, 95% CI = 0.970–0.996).…”

Section: Discussionmentioning

confidence: 68%

“…On the contrary, another study failed to detect an association with long sleep in 316 patients with nAMD compared to 500 patients without AMD ( Khurana et al, 2016 ). Besides, a MR study based on the neurodegenerative disorders, including age-related macular degeneration (AMD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson’s disease (PD), have not revealed relationships among the sleep duration and AMD (IVW P -value = 0.15) ( Grover et al, 2022 ). In the current study, we found that sleep duration influences the risk of AMD, that is, longer sleep duration reduces the risk of AMD while shorter sleep duration increases the risk of AMD.…”

Section: Discussionmentioning

confidence: 99%

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Minimal effect of sleep on the risk of age-related macular degeneration: a Mendelian randomization study

Zhu,

Li,

et al. 2023

Front. Aging Neurosci.

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AimsObservational studies have shown that sleep pattern is associated with age-related macular degeneration (AMD), but whether sleep pattern is a causal factor for AMD remains unclear. This study aims to use Mendelian randomization (MR) analysis to investigate the potential causal relationship between sleep traits and AMD.MethodsThis is a two-sample MR study. The single-nucleotide polymorphisms associated with AMD and early AMD were selected as the outcome from two different genome-wide association studies (GWAS): the early AMD GWAS with 14,034 cases and 91,214 controls, and AMD GWAS with 3,553 cases and 147,089 controls. The datasets of sleep duration, daytime dozing, and sleeplessness were used as exposure, which comprised nearly 0.46 million participants. Inverse-variance weighted method was used as the main result, and comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the impact of potential horizontal pleiotropy.ResultsThrough MR analysis, we found that sleep duration was significantly associated with AMD (OR = 0.983, 95% CI = 0.970–0.996, P-value = 0.01). We also found suggestive evidence for the association of genetically predicted sleep duration with early AMD, which showed a consistent direction of effect with a marginal significance (OR = 0.724, 95% CI = 0.503–1.041, P-value = 0.08). Sensitivity analyses further supported the robustness of the causal relationship between sleep duration and AMD. However, we were unable to determine the relationship between daytime dozing or sleeplessness and AMD (including early AMD) (P-value > 0.05).ConclusionSleep duration affects the causal risk for AMD; that is, longer sleep duration reduces the risk of AMD, while shorter sleep duration increases the risk of AMD. Although the influence is minimal, keeping adequate sleep duration is recommended, especially for patients with intermediate or advanced AMD.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Minimal effect of sleep on the risk of age-related macular degeneration: a Mendelian randomization study

Zhu,

Li,

et al. 2023

Front. Aging Neurosci.

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“…These two MR estimates all passed Bonferroni correction (IVW-derived P < 8.33 × 10 –3 , significant). A previous study has used MR approaches to evaluate the effect of SSD and LSD on advanced AMD ( Grover and Sharma, 2022 ) and found no significant effects. The leave-one-out plots ( Supplementary Figure 1 ), the funnel plots ( Supplementary Figure 2 ), the MR-Egger intercept test, Cochran’s Q test, and MR-PRESSO global test ( Table 5 ) all suggested no apparent heterogeneity or pleiotropy in these results.…”

Section: Resultsmentioning

confidence: 99%

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

Lei,

Liu,

2023

Front. Aging Neurosci.

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PurposeTo investigate the association between sleep duration and age-related macular degeneration (AMD).DesignCross-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.MethodsThe 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.ResultsIn 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).ConclusionOur 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.

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“…AMD, a representative disease in geriatric ophthalmology, is a well-known disease with heritable characteristics, which was the initial focus of GWAS research [66][67][68][69][70]. With these genomic data, MR-based causal studies of dyslipidaemia or other risk factors for AMD have been conducted [71][72][73][74][75][76]. In addition, the C-reactive protein is a hallmark lipid in drusen [77].…”

Section: Discussionmentioning

confidence: 99%

Causal Associations of Glaucoma and Age-Related Macular Degeneration with Cataract: A Bidirectional Two-Sample Mendelian Randomisation Study

Seo,

Lee

2024

Genes

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Common age-related eye disorders include glaucoma, cataract, and age-related macular degeneration (AMD); however, little is known about their relationship with age. This study investigated the potential causal relationship between glaucoma and AMD with cataract using genetic data from multi-ethnic populations. Single-nucleotide polymorphisms (SNPs) associated with exposure to cataract were selected as instrumental variables (IVs) from genome-wide association studies using meta-analysis data from BioBank Japan and UK Biobank. A bidirectional two-sample Mendelian randomisation (MR) study was conducted to assess the causal estimates using inverse variance weighted, MR-Egger, and MR pleiotropy residual sum and outlier tests. SNPs with (p < 5.0 × 10−8) were selected as IVs for cataract, primary open-angle glaucoma, and AMD. We found no causal effects of cataract on glaucoma or AMD (all p > 0.05). Furthermore, there were no causal effects of AMD on cataract (odds ratio [OR] = 1.02, p = 0.400). However, glaucoma had a substantial causal effect on cataract (OR = 1.14, p = 0.020). Our study found no evidence for a causal relationship of cataract on glaucoma or AMD and a casual effect of AMD on cataract. Nonetheless, glaucoma demonstrates a causal link with cataract formation, indicating the need for future investigations of age-related eye diseases.

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Sleep, Pain, and Neurodegeneration: A Mendelian Randomization Study

Cited by 11 publications

References 51 publications

Minimal effect of sleep on the risk of age-related macular degeneration: a Mendelian randomization study

Minimal effect of sleep on the risk of age-related macular degeneration: a Mendelian randomization study

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

Causal Associations of Glaucoma and Age-Related Macular Degeneration with Cataract: A Bidirectional Two-Sample Mendelian Randomisation Study

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