Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (8): 109-114.doi: 10.6040/j.issn.1671-7554.0.2022.0290

Previous Articles     Next Articles

Mendelian randomization study of sleep phenotypes and irritable bowel syndrome

ZHANG Kai1,2, SI Shucheng1,2, LI Jiqing1,2, LIU Xiaowen1,2, ZHAO Yingqi1,2, XUE Fuzhong1,2   

  1. 1. Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250002, Shandong, China;
    2. Institute for Medical Dataology, Shandong University, Jinan 250012, Shandong, China
  • Published:2022-07-27

PDF (PC)

304

Abstract: Objective To explore the causal relationship between sleep phenotypes and irritable bowel syndrome(IBS). Methods Mutually independent genetic variants closely related to sleep phenotypes were chosen as instrumental variables from the genome-wide association study database(GWAS)and the Finnish Biobank database(FinnGen). With odds ratio(OR)as an outcome indicator, the causal relationship between sleep phenotypes and IBS was analyzed using MR methods, including inverse-variance weighted(MR-IVW), weighted median, simple median method, robust adjusted contour score method, pleiotropic residual sum, and heterogeneity. Results MR-IVW results showed that short sleep duration and insomnia led to an increased risk of IBS by 147%(OR=2.47, 95%CI: 1.13-5.41)and 18% (OR=1.18, 95%CI: 1.14-1.22), respectively. Morning habits were associated with a 12% lower risk of IBS(OR=0.88, 95%CI: 0.84-0.92). The results of external data validation showed that only insomnia was associated with a statistically significant risk of IBS(P<0.001). After relevant covariates were adjusted with multivariate MR methods, the association effect between insomnia and IBS remained statistically significant(P<0.001). Conclusion Short sleep duration and insomnia will increase the risk of IBS.

Key words: Sleep phenotypes, Insomnia, Irritable bowel syndrome, Mendelian randomization, Causal inference

CLC Number: 

  • R714.8
[1] 高炼, 黄晓明, 吴清明. 肠易激综合征治疗与预防的研究进展[J]. 中国全科医学, 2022, 25(9): 1148-1154. GAO Lian, HUANG Xiaoming, WU Qingming. Recent developments in the prevention and treatment of irritable bowel syndrome[J]. Chinese General Practice, 2022, 25(9): 1148-1154.
[2] 胡敏, 刘诗. 肠易激综合征[J]. 临床消化病杂志, 2012, 24(2): 103-104. HU Min, LIU Shi. Irritable bowel syndrome[J]. Chinese Journal of Clinical Gastroenterology, 2012, 24(2): 103-104.
[3] Ford AC, Lacy BE, Talley NJ. Irritable bowel syndrome [J]. N Engl J Med, 2017, 376(26): 2566-2578.
[4] Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review [J]. JAMA, 2015, 313(9): 949-958.
[5] Staudacher HM, Mikocka-Walus A, Ford AC. Common mental disorders in irritable bowel syndrome: pathophysiology, management, and considerations for future randomised controlled trials [J]. Lancet Gastroenterol Hepatol, 2021, 6(5): 401-410.
[6] Emdin CA, Khera AV, Kathiresan S. Mendelian randomization [J]. JAMA, 2017, 318(19): 1925-1926.
[7] Smith GD, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? [J]. Int J Epidemiol, 2003, 32(1): 1-22.
[8] Sekula P, Del Greco M F, Pattaro C, et al. Mendelian randomization as an approach to assess causality using observational data [J]. J Am Soc Nephrol, 2016, 27(11): 3253-3265.
[9] Dashti HS, Jones SE, Wood AR, et al. Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates [J]. Nat Commun, 2019, 10(1): 1100. doi: 10.1038/s41467-019-08917-4.
[10] Jones SE, Lane JM, Wood AR, et al. Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms [J]. Nat Commun, 2019, 10(1): 343. doi: 10.1038/s41467-018-08259-7.
[11] Campos AI, García-Marín LM, Byrne EM, et al. Insights into the aetiology of snoring from observational and genetic investigations in the UK Biobank [J]. Nat Commun, 2020, 11(1): 817. doi: 10.1038/s41467-020-14625-1.
[12] Dashti HS, Daghlas I, Lane JM, et al. Genetic determinants of daytime napping and effects on cardiometabolic health [J]. Nat Commun, 2021, 12(1): 900. doi: 10.1038/s41467-020-20585-3.
[13] Jansen PR, Watanabe K, Stringer S, et al. Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways [J]. Nat Genet, 2019, 51(3): 394-403.
[14] Eijsbouts C, Zheng T, Kennedy NA, et al. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders [J]. Nat Genet, 2021, 53(11): 1543-1552.
[15] Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data [J]. Genet Epidemiol, 2013, 37(7): 658-665.
[16] Bowden J, Davey Smith G, Haycock PC, et al. Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator [J]. Genet Epidemiol, 2016, 40(4): 304-314.
[17] Zhao Q, Wang J, Hemani G, et al. Statistical inference in two-sample summary-data mendelian randomization using robust adjusted profile score [J]. Ann. Statist, 2020, 48(3): 1742-1769.
[18] 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.
[19] Burgess S, Thompson SG. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects [J]. Am J Epidemiol, 2015, 181(4): 251-260.
[20] Lee SK, Yoon DW, Lee S, et al. The association between irritable bowel syndrome and the coexistence of depression and insomnia [J]. J Psychosom Res, 2017, 93: 1-5. doi: 10.1016/j.jpsychores.2016.12.007.
[21] Tu Q, Heitkemper MM, Jarrett ME, et al. Sleep disturbances in irritable bowel syndrome: a systematic review [J]. Neurogastroenterol Motil, 2017, 29(3). doi: 10.1111/nmo.12946.
[22] Rotem AY, Sperber AD, Krugliak P, et al. Polysomnographic and actigraphic evidence of sleep fragmentation in patients with irritable bowel syndrome [J]. Sleep, 2003, 26(6): 747-752.
[23] Fond G, Loundou A, Hamdani N, et al. Anxiety and depression comorbidities in irritable bowel syndrome(IBS): a systematic review and meta-analysis [J]. Eur Arch Psychiatry Clin Neurosci, 2014, 264(8): 651-660.
[24] Lee CG, Lee JK, Kang Y-S, et al. Visceral abdominal obesity is associated with an increased risk of irritable bowel syndrome [J]. Am J Gastroenterol, 2015, 110(2): 310-319.
[25] Talley NJ, Powell N, Walker MM, et al. Role of smoking in functional dyspepsia and irritable bowel syndrome: three random population-based studies [J]. Aliment Pharmacol Ther, 2021, 54(1): 32-42.
[26] Reding KW, Cain KC, Jarrett ME, et al. Relationship between patterns of alcohol consumption and gastrointestinal symptoms among patients with irritable bowel syndrome [J]. Am J Gastroenterol, 2013, 108(2): 270-276.
[27] Orr WC, Crowell MD, Lin B, et al. Sleep and gastric function in irritable bowel syndrome: derailing the brain-gut axis [J]. Gut, 1997, 41(3): 390-393.
[28] Palmblad J, Petrini B, Wasserman J, et al. Lymphocyte and granulocyte reactions during sleep deprivation [J]. Psychosom Med, 1979, 41(4): 273-278.
[29] Everson CA, Toth LA. Systemic bacterial invasion induced by sleep deprivation [J]. Am J Physiol Regul Integr Comp Physiol, 2000, 278(4): 905-916.
[30] Fry A, Littlejohns TJ, Sudlow C, et al. Comparison of sociodemographic and health-related characteristics of UK Biobank participants with those of the general population [J]. Am J Epidemiol, 2017, 186(9): 1026-1034.
[1] YANG Xuan, LI Yanzhi, MA Wei, JIA Chongqi. Causal influence of lung function on risk of fatality of COVID-19: a two-sample Mendelian randomization study [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 104-111.
[2] LI Yunxia, LI Hongkai, MA Yuntao, YU Yuanyuan, SUN Xiaoru, LIU Xinhui, SI Shucheng, HOU Lei, YUAN Tonghui, LIU Lu, LI Wenchao, XUE Fuzhong, LIU Yanxun. Causal association between height and risk of coronary heart disease: a two-sample Mendelian randomization analysis [J]. Journal of Shandong University (Health Sciences), 2020, 58(5): 107-114.
[3] SONG Limin, LU Shanshan, WANG Dawei, LÜ Xin, GAO Yuan, TANG Jiyou. Correlation between sleep architecture and attention and memory function in chronic insomniacs [J]. Journal of Shandong University (Health Sciences), 2019, 57(4): 52-58.
[4] LIU Xinhui, LI Hongkai, LI Mingzhuo, YU Yuanyuan, SI Shucheng, HOU Lei, LIU Lu, LI Wenchao, YUAN Tonghui, LI Yunxia, ZHOU Yuchang, XUE Fuzhong. A Mendelian randomization study on the causal relationship between waist circumference and incidence of coronary heart disease [J]. Journal of Shandong University (Health Sciences), 2019, 57(11): 103-109.
[5] LI Zhuqing, ZHANG Wenxue, LI Lixiang, WANG Peng, YU Yanbo, ZUO Xiuli, LI Yanqing. Sodium butyrate ameliorates visceral hypersensitivity by down-regulating IRAK1 in irritable bowel syndrome [J]. Journal of Shandong University (Health Sciences), 2018, 56(9): 23-28.
[6] ZHANG Wenxue, XU Lidong, ZHANG Mingming, GUO Chuanguo, ZUO Xiuli. NR2B contributes to visceral hypersensitivity in irritable bowel syndrome via mBDNF [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(7): 17-22.
[7] LI Qian, DAI Taoli, HAN Wei, GUO Chenghao. Role of vascular endothelial cell activation in the pathogenesis of post infectious irritable bowel syndrome [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(12): 58-61.
[8] DONG Yanyan, LI Yanqing, ZUO Xiuli, LI Changqing. Prevalence of irritable bowel syndrome and functional constipation  in college students from a university in Shandong Province [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(6): 122-125.
[9] SONG Dong-ling,WANG Meng-xin,ZENG Juan,LI Yan-qing. Effect of psychological treatment for patients with irritable bowel syndrome [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(10): 1068-1071.
[10] GUOMin,LIYAn-qing,LIUChuan-yong,XIEDong-ping,GUOYU-ting,ZUOXiu-li,ZENGJuan. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(5): 514-518.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] MA Qingyuan, PU Peidong, HAN Fei, WANG Chao, ZHU Zhoujun, WANG Weishan, SHI Chenhui. Effect of miR-27b-3p regulating SMAD1 on osteosarcoma cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 32 -37 .
[2] SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1 -6 .
[3] LONG Tingting, XIE Ming, ZHOU Lu, ZHU Junde. Effect of Noggin protein on learning and memory abilities and the dentate gyrus structure after cerebral ischemia reperfusion injury in mice[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 15 -23 .
[4] LI Ning, LI Juan, XIE Yan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression of LncRNA AL109955.1 in 80 cases of colorectal cancer and its effect on cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 38 -46 .
[5] ZHANG Baowen, LEI Xiangli, LI Jinna, LUO Xiangjun, ZOU Rong. miR-21-5p targeted TIMP3 to inhibit proliferation and extracellular matrix accumulation of mesangial cells in Type II diabetic nephropathy mice[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 7 -14 .
[6] FU Jieqi, ZHANG Man, ZHANG Xiaolu, LI Hui, CHEN Hong. Molecular mechanism of Toll-like receptor 4 in the aggravation of blood lipid accumulation by inhibiting the peroxisome proliferator-activate receptor γ[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 24 -31 .
[7] XU Yuxiang, LIU Yudong, ZHANG Peng, DUAN Ruisheng. A retrospective analysis of risk factors of cerebral microbleeds in 101 patients with cerebral small vessel disease[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 67 -71 .
[8] DING Xiangyun, YU Qingmei, ZHANG Wenfang, ZHUANG Yuan, HAO Jing. Correlation of the expression of insulin-like growth factor II in granulosa cells and ovulation induction outcomes of 84 patients with polycystic ovary syndrome[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 60 -66 .
[9] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47 -52 .
[10] XIAO Juan, XIAO Qiang, CONG Wei, LI Ting, DING Shouluan, ZHANG Yuan, SHAO Chunchun, WU Mei, LIU Jianing, JIA Hongying. Comparison of diagnostic efficacy of two kinds of thyroid imagine reporting and data systems[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 53 -59 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd