Evaluating the Bidirectional Causal Association Between Daytime Napping and Alzheimer’s Disease Using Mendelian Randomization

Article type: Research Article

Authors: Li, Sijie^{a; b} | Liu, Bian^c | Li, Qing-hao^d | Zhang, Yan^e | Zhang, Haihua^b | Gao, Shan^b | Wang, Longcai^f | Wang, Tao^g | Han, Zhifa^h | Liu, Guiyou^{b; g; i; j; *} | Wang, Kun^{d; *}

Affiliations: [a] Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing, China | [b] Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Centerfor Brain Disorders, Capital Medical University, Beijing, China | [c] Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China | [d] Children’s Center, the Affiliated Taian City Centeral Hospital of Qingdao University, Taian, Shandong, China | [e] Department of Pathology, The Affiliated Hospital of Weifang Medical University, Weifang, China | [f] Department of Anesthesiology, TheAffiliated Hospital of Weifang Medical University, Weifang, China | [g] Chinese Institute for Brain Research, Beijing, China | [h] State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China | [i] Key Laboratory of Cerebral Microcirculation in Universities of Shandong; Department of Neurology, Second Affiliated Hospital; Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, China | [j] Beijing Key Laboratory of Hypoxia Translational Medicine, National Engineering Laboratory of Internet Medical Diagnosis and Treatment Technology, Xuanwu Hospital, Capital Medical University, Beijing, China

Correspondence: [*] Correspondence to: Guiyou Liu, Beijing Institute for Brain Disorders, Capital Medical University, Room 725, Morphology Building, No.10, Xitoutiao, You’an Men Wai, Fengtai District, Beijing 100069, China. E-mail: liuguiyou1981@163.com and Kun Wang, Children’s Center, the Affiliated Taian City Centeral Hospital of Qingdao University, Taian, Shandong, 271000, China. E-mail: wktawx@163.com.

Abstract: Background:Until now, both cross-sectional and longitudinal studies have identified controversial findings about the association between daytime napping and Alzheimer’s disease (AD) or cognitive decline. Therefore, it remains unclear about the causal association between daytime napping and AD or cognitive decline. Objective:We aim to investigate the causal association between daytime napping and AD. Methods:Here, we conduct a bidirectional Mendelian randomization (MR) analysis to investigate the causal association between daytime napping and AD using large-scale GWAS datasets from daytime napping including 452,633 individuals of European ancestry and AD including 35,274 AD and 59,163 controls of European ancestry. A total of five MR methods are selected including inverse-variance weighted (IVW), weighted median, MR-Egger, MR-PRESSO, and contamination mixture method. Results: MR analysis highlights significant causal association of AD with daytime napping using IVW (beta = -0.006, 95% CI [–0.009, –0.002], p = 2.00E-03), but no significant causal association of daytime napping with AD using IVW (OR = 0.76, 95% CI 0.53-1.10, p = 1.40E-01). Conclusion:Our bidirectional MR analysis demonstrates the causal effect of AD on daytime napping. However, there is no causal effect of daytime napping on AD. Our current findings are consistent with recent evidence from other MR studies that highlight little evidence supporting a causal effect of sleep traits on AD and support the causal effect of AD on sleep traits.

Keywords: Alzheimer’s disease, daytime napping, genome-wide association study, Mendelian randomization

DOI: 10.3233/JAD-220497

Journal: Journal of Alzheimer's Disease, vol. 89, no. 4, pp. 1315-1322, 2022