The causal relationship between daytime nap and non-alcoholic fatty liver disease: a two-sample mendelian randomization analysis

Abstract

Abstract: Objective To explore the causal relationship between daytime nap and the risk of non-alcoholic fatty liver disease by using two sample Mendelian randomization analysis. Methods Dataset of daytime nap and non-alcoholic fatty liver disease were obtained from the IEU Open GWAS database. Using the inverse variance weighting, MR Egger, and weighted median methods to explore the causal relationship between daytime nap and non-alcoholic fatty liver disease, and using Cochran's Q test, MR Egger regression, MR-PRESSO, Leave one out, funnel plot, and forest plot methods to evaluate the stability and reliability of the research results. Results The causal effects obtained by the three methods were consistent, and the inverse variance weighting method had statistical significance (OR=2.166, 95% CI=1.274~3.684, P=0.004). The results of WME analysis (OR=1.643, 95%CI=0.758~3.564, P=0.209). MR-Egger regression showed (OR=4.201, 95%CI=0.591~29.863, P=0.155). IVW test (Q=105.474, P=0.217) and MR-Egger test (Q=104.946, P=0.207) results did not show significant heterogeneity. MR-PRESSO analysis (P=0.246) and MR-Egger regression analysis (P=0.493) did not support the presence of horizontal pleiotropy, and the findings were robust. Conclusion From a genetic perspective, this study preliminarily revealed a positive causal relationship between nap time and the risk of non-alcoholic fatty liver disease.

Key words: Daytime nap, Nonalcoholic fatty liver disease, Mendelian randomization

WANG Ji-cai, ZHANG Guang-quan, WU Fen-fang, SHI Xian-jie. The causal relationship between daytime nap and non-alcoholic fatty liver disease: a two-sample mendelian randomization analysis[J]. Chinese Hepatolgy, 2025, 30(12): 1695-1699.

References

[1] Sheka A C, Adeyi O, Thompson J, et al. Nonalcoholic steatohepatitis: a review[J]. JAMA, 2020,323(12):1175-1183.
[2] Younossi Z M, Koenig A B, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016,64(1):73-84.
[3] Rinella M E, Neuschwander-Tetri B A, Siddiqui M S, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease[J]. Hepatology, 2023,77(5):1797-1835.
[4] Tan D, Ng C H, Lin S Y, et al. Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis[J]. Lancet Oncol, 2022,23(4):521-530.
[5] Younossi Z M, Tampi R, Priyadarshini M, et al. Burden of illness and economic model for patients with nonalcoholic steatohepatitis in the United States[J]. Hepatology, 2019,69(2):564-572.
[6] Estes C, Anstee Q M, Arias-Loste M T, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030[J]. J Hepatol, 2018,69(4):896-904.
[7] Halson S L. Sleep in elite athletes and nutritional interventions to enhance sleep[J]. Sports Med, 2014,44 Suppl 1(Suppl 1):S13-S23.
[8] Xiao Q, Arem H, Moore S C, et al. A large prospective investigation of sleep duration, weight change, and obesity in the NIH-AARP Diet and Health Study cohort[J]. Am J Epidemiol, 2013,178(11):1600-1610.
[9] Cappuccio F P, Cooper D, D′Elia L, et al. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies[J]. Eur Heart J, 2011,32(12):1484-1492.
[10] Woolf B, Di Cara N, Moreno-Stokoe C, et al. Investigating the transparency of reporting in two-sample summary data Mendelian randomization studies using the MR-Base platform[J]. Int J Epidemiol, 2022,51(6):1943-1956.
[11] Burgess S, Davey Smith G, Davies N M, et al. Guidelines for performing Mendelian randomization investigations: update for summer 2023[J]. Wellcome Open Res, 2019,4:186.
[12] Dashti H S, Daghlas I, Lane J M, et al. Genetic determinants of daytime napping and effects on cardiometabolic health[J]. Nat Commun, 2021,12(1):900.
[13] Chen S, Hu Z, He L, et al. Relationship between daytime napping and cardiovascular disease: a two-sample mendelian randomization study[J]. Hellenic J Cardiol, 2024,75:26-31.
[14] Evans D M, Davey Smith G. Mendelian randomization: new applications in the coming age of hypothesis-free causality[J]. Annu Rev Genomics Hum Genet, 2015,16:327-350.
[15] Cui Z, Feng H, He B, et al. Relationship between serum amino acid levels and bone mineral density: a Mendelian randomization study[J]. Front Endocrinol (Lausanne), 2021,12:763538.
[16] Kamat M A, Blackshaw J A, Young R, et al. PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations[J]. Bioinformatics, 2019,35(22):4851-4853.
[17] Bowden J, Davey Smith G, Haycock P C, et al. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator[J]. Genet Epidemiol, 2016,40(4):304-314.
[18] Luo P, Yuan Q, Wan X, et al. A two-sample Mendelian randomization study of circulating lipids and deep venous thrombosis[J]. Sci Rep, 2023,13(1):7432.
[19] Bowden J, Del Greco M F, Minelli C, et al. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization[J]. Stat Med, 2017,36(11):1783-1802.
[20] Burgess S, Thompson S G. Interpreting findings from Mendelian randomization using the MR-Egger method[J]. Eur J Epidemiol, 2017,32(5):377-389.
[21] Hemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome[J]. Elife, 2018,7:e34408.
[22] Verbanck M, Chen C Y, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases[J]. Nat Genet, 2018,50(5):693-698.
[23] Huang T D, Behary J, Zekry A. Non-alcoholic fatty liver disease: a review of epidemiology, risk factors, diagnosis and management[J]. Intern Med J, 2020,50(9):1038-1047.
[24] Qu H, Wang H, Deng M, et al. Associations between longer habitual day napping and non-alcoholic fatty liver disease in an elderly Chinese population[J]. PLoS One, 2014,9(8):e105583.
[25] Hong C, Wu C, Ma P, et al. Positive association of nap duration with risk of non-alcoholic fatty liver disease in an occupational population in Guangdong Province, China: a cross-sectional study[J]. BMC Gastroenterol, 2022,22(1):185.
[26] Fang W, Li Z, Wu L, et al. Longer habitual afternoon napping is associated with a higher risk for impaired fasting plasma glucose and diabetes mellitus in older adults: results from the Dongfeng-Tongji cohort of retired workers[J]. Sleep Med, 2013,14(10):950-954.
[27] Laposky A D, Bass J, Kohsaka A, et al. Sleep and circadian rhythms: key components in the regulation of energy metabolism[J]. FEBS Lett, 2008,582(1):142-151.