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

Rong-Cheng Zhu; Fen-Fen Li; Yi-Qing Wu; Quan-Yong Yi; Xiu-Feng Huang

doi:10.3389/fnagi.2023.1159711

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

Front Aging Neurosci. 2023 Aug 21:15:1159711. doi: 10.3389/fnagi.2023.1159711. eCollection 2023.

Authors

Rong-Cheng Zhu^#¹, Fen-Fen Li^#^{2

3}, Yi-Qing Wu⁴, Quan-Yong Yi⁵, Xiu-Feng Huang¹

Affiliations

¹ Zhejiang Provincial Clinical Research Center for Pediatric Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
² National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
³ State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
⁴ Department of Pediatrics, The Second School of Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁵ The Affiliated Ningbo Eye Hospital of Wenzhou Medical University, Ningbo, Zhejiang, China.

^# Contributed equally.

Abstract

Aims: Observational 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.

Methods: This 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.

Results: Through 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).

Conclusion: Sleep 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.

Keywords: Mendelian randomization; age-related macular degeneration; causal inference; genetic instrument; sleep duration.

Grants and funding

This study was supported by the Zhejiang Provincial Natural Science Foundation of China (LGF22H120013 and LY22H120008), the Zhejiang Provincial Clinical Research Center for Pediatric Disease (2022E50003), and the National Natural Science Foundation of China (82070981 and 82201229).