Sleep, pain, and neurodegeneration: A Mendelian randomization study

Grover, Sandeep; Sharma, Manu

doi:10.1101/2021.03.08.21253133

Cited by 2 publications

(1 citation statement)

References 83 publications

(99 reference statements)

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“…Thus, a relationship between macular thickness and melatonin may help explain a circadian influence of macular traits on chronotype. A recent MR study linked a morning chronotype to age-related macular degenration [69]. Elevated melatonin was also obsered in myopic adults, and in a juvenile population myopia was increased with an intermediate or evening chronotype compared to morning [70,71].…”

Section: Gwas Trait Enrichment Suggest Exogenous Influence Of Chronotypementioning

confidence: 98%

Genetically mediated associations between chronotype and neuroimaging phenotypes in the UK Biobank: a Mendelian randomisation study

Williams,

Russ,

Bravo-Merodio

et al. 2023

Preprint

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Chronotype impacts numerous physiological and disease traits, from metabolic syndrome to schizophrenia. The suprachiasmatic nucleus (SCN) maintains transcriptional-translational feedback loop (TTFL) which acts as a central chronobiological pacemaker, regulating 24-hour cycles throughout the human body. However, each tissue maintains its own peripheral clock, and both endogenous hormones and neurotransmitters and exogenous environmental cues regulate the SCN’s central clock. The extent to which brain regions outside the SCN influence the core TTFL is unknown. Here, we investigated how genetic variability affecting brain regions outside the SCN may indirectly influence chronotype, using Mendelian randomization and causal inference. We performed genome wide association studies (GWAS) based on image derived phenotypes (IDPs) from neuroimaging data (grey matter volume, thickness and surface area, microstructural white matter measures; 42,062 participants), and additionally for sleep duration and morning/evening chronotype (361,739 participants). Significant, single nucleotide polymorphisms (SNPs) associating with each phenotype were entered into 2-sample Mendelian randomization performed using inverse-variance weighted methods (exposure versus outcome): 1) chronotype versus each IDP, 2) sleep versus each IDP and 3) each IDP versus chronotype. Subsequently, we investigated genes where significant instrumental SNPs were located for circadian periodic cycling, interaction with TTFL genes in common biological pathways (genetic, physical, or functional interaction), and enrichment of traits from UK Biobank and GWAS Catalogs. We found three associations with chronotype (morning/evening diurnal preference) outside the SCN based on genetically predicted (FAM76B, DENND1A, CDH11) regional differences in brain volume. Specifically, genetically predicted lower inferior temporal gyrus volume linked to morning phenotype, while lower volume of the superior parietal lobule and angular gyrus linked to evening preference. In addition, evening chronotype exposure influenced superior temporal gyrus volume, and both increased sleep duration and evening chronotype influenced thalamic volume. We conclude that genetically mediated associations between chronotype and brain regions outside SCN exist suggesting novel zeitgeber mechanisms.

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Section: Gwas Trait Enrichment Suggest Exogenous Influence Of Chronotypementioning

confidence: 98%

Genetically mediated associations between chronotype and neuroimaging phenotypes in the UK Biobank: a Mendelian randomisation study

Williams,

Russ,

Bravo-Merodio

et al. 2023

Preprint

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Is there an association between daytime napping, cognitive function and brain volume? A Mendelian randomisation study in the UK Biobank

Paz

Dashti

Garfield

2021

Preprint

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Background: Daytime napping has been associated with cognitive function in observational studies. However, it remains elusive whether napping could be beneficial or detrimental for cognition and whether these associations are causal. Methods: Using Mendelian randomisation (MR), we studied the relationship between daytime napping and cognitive outcomes. Data were from UK Biobank (n= 378,932; mean age= 57 years). Our exposure (daytime napping) was instrumented using 92 genome-wide, independent genetic variants and our cognitive outcomes were reaction time and visual memory. Inverse-variance weighted MR was implemented, with sensitivity analyses including MR-Egger and the Weighted Median Estimator for horizontal pleiotropy. We also tested different daytime napping instruments (47 SNPs, 86 SNPs and 17 SNPs) to ensure the robustness of our results. Results: No associations were found between daytime napping and reaction time (expβ=1.01, 95%CI=1.00; 1.03), or visual memory (expβ=0.99, 95%CI=0.94; 1.05). MR-Egger and Weighted Median Estimator approaches showed no evidence of horizontal pleiotropy. Additional analyses with 47 SNPs (adjusted for excessive daytime sleepiness), 86 SNPs (excluding sleep apnoea) and 17 SNPs (no sample overlap with UKB) also showed no associations with reaction time or visual memory. Conclusions: Overall, we observed no evidence of a causal association between habitual daytime napping and reaction time and visual memory. Future studies should focus on the associations between napping and other cognitive outcomes.

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Sleep, pain, and neurodegeneration: A Mendelian randomization study

Cited by 2 publications

References 83 publications

Genetically mediated associations between chronotype and neuroimaging phenotypes in the UK Biobank: a Mendelian randomisation study

Genetically mediated associations between chronotype and neuroimaging phenotypes in the UK Biobank: a Mendelian randomisation study

Is there an association between daytime napping, cognitive function and brain volume? A Mendelian randomisation study in the UK Biobank

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