Causal Relationships Between Circulating Inflammatory Proteins and Obstructive Sleep Apnea: A Bidirectional Mendelian Randomization Study

References

• Lévy P, Kohler M, McNicholas WT, et al. Obstructive sleep apnoea syndrome. Nat Rev Dis Primers. 2015;1:15015. doi:10.1038/nrdp.2015.15
   PubMed Web of Science ®Google Scholar
• Benjafield AV, Ayas NT, Eastwood PR, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019;7(8):687–698. doi:10.1016/s2213-2600(19)30198-5
   PubMed Web of Science ®Google Scholar
• Franklin KA, Lindberg E. Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea. J Thorac Dis. 2015;7(8):1311–1322. doi:10.3978/j.issn.2072-1439.2015.06.11
   PubMed Web of Science ®Google Scholar
• Unnikrishnan D, Jun J, Polotsky V. Inflammation in sleep apnea: an update. Rev Endocr Metab Disord. 2015;16(1):25–34. doi:10.1007/s11154-014-9304-x
   PubMed Web of Science ®Google Scholar
• Ciccone MM, Scicchitano P, Zito A, et al. Correlation between inflammatory markers of atherosclerosis and carotid intima-media thickness in Obstructive Sleep Apnea. Molecules. 2014;19(2):1651–1662. doi:10.3390/molecules19021651
   PubMed Web of Science ®Google Scholar
• Unüvar Doğan F, Yosunkaya S, Kuzu Okur H, Can U. Relationships between Obstructive Sleep Apnea Syndrome, Continuous Positive Airway Pressure Treatment, and Inflammatory Cytokines. Sleep Disord. 2014;2014:518920. doi:10.1155/2014/518920
   PubMedGoogle Scholar
• Stradling JR, Craig SE, Kohler M, et al. Markers of inflammation: data from the MOSAIC randomised trial of CPAP for minimally symptomatic OSA. Thorax. 2015;70(2):181–182. doi:10.1136/thoraxjnl-2014-205958
   PubMed Web of Science ®Google Scholar
• Pau MC, Zinellu A, Mangoni AA, et al. Evaluation of Inflammation and Oxidative Stress Markers in Patients with Obstructive Sleep Apnea (OSA). J Clin Med. 2023;12(12):3935. doi:10.3390/jcm12123935
   PubMed Web of Science ®Google Scholar
• Smith GD, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32(1):1–22. doi:10.1093/ije/dyg070
   PubMed Web of Science ®Google Scholar
• Hartwig FP, Davies NM, Hemani G, Davey Smith G. Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique. Int J Epidemiol. 2016;45(6):1717–1726. doi:10.1093/ije/dyx028
   PubMed Web of Science ®Google Scholar
• Xu H, Liu F, Li Z, et al. Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals. Am J Respir Crit Care Med. 2022;206(12):1534–1545. doi:10.1164/rccm.202109-2044OC
   PubMed Web of Science ®Google Scholar
• Strausz S, Ruotsalainen S, Ollila HM, et al. Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health. Eur Respir J. 2021;57(5):2003091. doi:10.1183/13993003.03091-2020
   PubMed Web of Science ®Google Scholar
• Yi M, Zhao W, Fei Q, et al. Causal analysis between altered levels of interleukins and obstructive sleep apnea. Front Immunol. 2022;13:888644. doi:10.3389/fimmu.2022.888644
   PubMed Web of Science ®Google Scholar
• Yi M, Zhao W, Tan Y, et al. The causal relationships between obstructive sleep apnea and elevated CRP and TNF-α protein levels. Ann Med. 2022;54(1):1578–1589. doi:10.1080/07853890.2022.2081873
   PubMed Web of Science ®Google Scholar
• Emdin CA, Khera AV, Kathiresan S. Mendelian Randomization. JAMA. 2017;318(19):1925–1926. doi:10.1001/jama.2017.17219
   PubMed Web of Science ®Google Scholar
• Zhao JH, Stacey D, Eriksson N, et al. Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets. Nat Immunol. 2023;24(9):1540–1551. doi:10.1038/s41590-023-01588-w
   PubMed Web of Science ®Google Scholar
• Kurki MI, Karjalainen J, Palta P, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613(7944):508–518. doi:10.1038/s41586-022-05473-8
   PubMed Web of Science ®Google Scholar
• Zhang J, Chen X, Zhu Y, Wan S, Hu S, Yang Y. Investigating the Causal Relationship Between Sleep Behaviors and Primary Open-Angle Glaucoma: A Bidirectional Two-Sample Mendelian Randomization Study. Nat Sci Sleep. 2024;16:143–153. doi:10.2147/NSS.S439274
   PubMed Web of Science ®Google Scholar
• Li P, Wang H, Guo L, et al. Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study. BMC Med. 2022;20(1):443. doi:10.1186/s12916-022-02657-x
   PubMed Web of Science ®Google Scholar
• Gu Y, Jin Q, Hu J, et al. Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study. J Transl Med. 2023;21(1):357. doi:10.1186/s12967-023-04165-9
   PubMed Web of Science ®Google Scholar
• Wang C, Zhu D, Zhang D, et al. Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study. BMC Psychiatry. 2023;23(1):590. doi:10.1186/s12888-023-05081-4
   PubMed Web of Science ®Google Scholar
• Xiang M, Wang Y, Gao Z, et al. Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization. Front Immunol. 2023;13:985729. doi:10.3389/fimmu.2022.985729
   PubMed Web of Science ®Google Scholar
• Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658–665. doi:10.1002/gepi.21758
   PubMed Web of Science ®Google Scholar
• Papadimitriou N, Dimou N, Tsilidis KK, et al. Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis. Nat Commun. 2020;11(1):597. doi:10.1038/s41467-020-14389-8
   PubMed Web of Science ®Google Scholar
• Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–525. doi:10.1093/ije/dyv080
   PubMed Web of Science ®Google Scholar
• Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693–698. doi:10.1038/s41588-018-0099-7
   PubMed Web of Science ®Google Scholar
• Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement. JAMA. 2021;326(16):1614–1621. doi:10.1001/jama.2021.18236
   PubMed Web of Science ®Google Scholar
• Javaheri S, Barbe F, Campos-Rodriguez F, et al. Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences. J Am Coll Cardiol. 2017;69(7):841–858. doi:10.1016/j.jacc.2016.11.069
   PubMed Web of Science ®Google Scholar
• Mateika JH, Syed Z. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans: present knowledge and future investigations. Respir Physiol Neurobiol. 2013;188(3):289–300. doi:10.1016/j.resp.2013.04.010
   PubMed Web of Science ®Google Scholar
• Chen B, Liu YN, Ji L, et al. Elevated levels of interleukin-35 and interleukin-37 in adult patients with obstructive sleep apnea. J Clin Lab Anal. 2021;35(6):e23790. doi:10.1002/jcla.23790
   PubMed Web of Science ®Google Scholar
• Motamedi V, Kanefsky R, Matsangas P, et al. Elevated tau and interleukin-6 concentrations in adults with obstructive sleep apnea. Sleep Med. 2018;43:71–76. doi:10.1016/j.sleep.2017.11.1121
   PubMed Web of Science ®Google Scholar
• Chuang LP, Wu HP, Lee LA, et al. Elevated Monocytic Interleukin-8 Expression under Intermittent Hypoxia Condition and in Obstructive Sleep Apnea Patients. Int J Mol Sci. 2021;22(21):11396. doi:10.3390/ijms222111396
   PubMed Web of Science ®Google Scholar
• Yamaguchi Y, Fujio K, Shoda H, et al. IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis. J Immunol. 2007;179(10):7128–7136. doi:10.4049/jimmunol.179.10.7128
   PubMed Web of Science ®Google Scholar
• Ramirez-Carrozzi V, Sambandam A, Luis E, et al. IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nat Immunol. 2011;12(12):1159–1166. doi:10.1038/ni.2156
   PubMed Web of Science ®Google Scholar
• Nies JF, Panzer U. IL-17C/IL-17RE: Emergence of a Unique Axis in TH17 Biology. Front Immunol. 2020;11:341. doi:10.3389/fimmu.2020.00341
   PubMed Web of Science ®Google Scholar
• Vella G, Ritzmann F, Wolf L, et al. IL-17C contributes to NTHi-induced inflammation and lung damage in experimental COPD and is present in sputum during acute exacerbations. PLoS One. 2021;16(1):e0243484. doi:10.1371/journal.pone.0243484
   PubMed Web of Science ®Google Scholar
• White GE, Iqbal AJ, Greaves DR. CC chemokine receptors and chronic inflammation--therapeutic opportunities and pharmacological challenges. Pharmacol Rev. 2013;65(1):47–89. doi:10.1124/pr.111.005074
   PubMed Web of Science ®Google Scholar
• Hayashi M, Iwashita M, Nishimura Y, et al. Adipose-specific C-C motif chemokine ligand (CCL) 19 overexpression drives the mice to both insulin resistance and weight gain. BMJ Open Diabetes Res Care. 2021;9(1):e001871. doi:10.1136/bmjdrc-2020-001871
   PubMed Web of Science ®Google Scholar
• Yan Y, Zhao W, Liu W, et al. CCL19 enhances CD8+ T-cell responses and accelerates HBV clearance. J Gastroenterol. 2021;56(8):769–785. doi:10.1007/s00535-021-01799-8
   PubMed Web of Science ®Google Scholar
• Wu X, Sun M, Yang Z, et al. The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases. Front Cell Dev Biol. 2021;9:686548. doi:10.3389/fcell.2021.686548
   PubMed Web of Science ®Google Scholar
• Yokoyama W, Kohsaka H, Kaneko K, et al. Abrogation of CC chemokine receptor 9 ameliorates collagen-induced arthritis of mice. Arthritis Res Ther. 2014;16(5):445. doi:10.1186/s13075-014-0445-9
   PubMed Web of Science ®Google Scholar
• Wurbel MA, McIntire MG, Dwyer P, Fiebiger E. CCL25/CCR9 interactions regulate large intestinal inflammation in a murine model of acute colitis. PLoS One. 2011;6(1):e16442. doi:10.1371/journal.pone.0016442
   PubMed Web of Science ®Google Scholar
• López-Pacheco C, Soldevila G, Du Pont G, Hernández-Pando R, García-Zepeda EA. CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation. Mediators Inflamm. 2016;2016:3635809. doi:10.1155/2016/3635809
   PubMed Web of Science ®Google Scholar
• Hieshima K, Ohtani H, Shibano M, et al. CCL28 has dual roles in mucosal immunity as a chemokine with broad-spectrum antimicrobial activity. J Immunol. 2003;170(3):1452–1461. doi:10.4049/jimmunol.170.3.1452
   PubMed Web of Science ®Google Scholar
• Cook DN. The role of MIP-1 alpha in inflammation and hematopoiesis. J Leukoc Biol. 1996;59(1):61–66. doi:10.1002/jlb.59.1.61
   PubMed Web of Science ®Google Scholar
• Terpos E, Politou M, Viniou N, Rahemtulla A. Significance of macrophage inflammatory protein-1 alpha (MIP-1alpha) in multiple myeloma. Leuk Lymphoma. 2005;46(12):1699–1707. doi:10.1080/10428190500175049
   PubMed Web of Science ®Google Scholar
• Hata H. Bone lesions and macrophage inflammatory protein-1 alpha (MIP-1a) in human multiple myeloma. Leuk Lymphoma. 2005;46(7):967–972. doi:10.1080/10428190500066636
   PubMed Web of Science ®Google Scholar
• Müller AK, Meyer M, Werner S. The roles of receptor tyrosine kinases and their ligands in the wound repair process. Semin Cell Dev Biol. 2012;23(9):963–970. doi:10.1016/j.semcdb.2012.09.015
   PubMed Web of Science ®Google Scholar
• Ornitz DM, Itoh N. The Fibroblast Growth Factor signaling pathway. Wiley Interdiscip Rev Dev Biol. 2015;4(3):215–266. doi:10.1002/wdev.176
   PubMed Web of Science ®Google Scholar
• Itoh N, Ornitz DM. Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease. J Biochem. 2011;149(2):121–130. doi:10.1093/jb/mvq121
   PubMed Web of Science ®Google Scholar
• Goetz R, Beenken A, Ibrahimi OA, et al. Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members. Mol Cell Biol. 2007;27(9):3417–3428. doi:10.1128/mcb.02249-06
   PubMed Web of Science ®Google Scholar
• Hotta Y, Nakamura H, Konishi M, et al. Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver. Endocrinology. 2009;150(10):4625–4633. doi:10.1210/en.2009-0119
   PubMed Web of Science ®Google Scholar
• Eiraku M, Hirata Y, Takeshima H, Hirano T, Kengaku M. Delta/notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like repeat-containing protein targeted to dendrites of developing and adult central nervous system neurons. J Biol Chem. 2002;277(28):25400–25407. doi:10.1074/jbc.M110793200
   PubMed Web of Science ®Google Scholar
• Eiraku M, Tohgo A, Ono K, et al. DNER acts as a neuron-specific Notch ligand during Bergmann glial development. Nat Neurosci. 2005;8(7):873–880. doi:10.1038/nn1492
   PubMed Web of Science ®Google Scholar
• Tohgo A, Eiraku M, Miyazaki T, et al. Impaired cerebellar functions in mutant mice lacking DNER. Mol Cell Neurosci. 2006;31(2):326–333. doi:10.1016/j.mcn.2005.10.003
   PubMed Web of Science ®Google Scholar
• Stirewalt DL, Radich JP. The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer. 2003;3(9):650–665. doi:10.1038/nrc1169
   PubMed Web of Science ®Google Scholar
• Ramos MI, Perez SG, Aarrass S, et al. FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis in rheumatoid arthritis. Arthritis Res Ther. 2013;15(6):R209. doi:10.1186/ar4403
   PubMed Web of Science ®Google Scholar
• Mouchemore KA, Pixley FJ. CSF-1 signaling in macrophages: pleiotrophy through phosphotyrosine-based signaling pathways. Crit Rev Clin Lab Sci. 2012;49(2):49–61. doi:10.3109/10408363.2012.666845
   PubMed Web of Science ®Google Scholar
• Saleh R, Lee MC, Khiew SH, et al. CSF-1 in Inflammatory and Arthritic Pain Development. J Immunol. 2018;201(7):2042–2053. doi:10.4049/jimmunol.1800665
   PubMed Web of Science ®Google Scholar
• Raman C. CD5, an important regulator of lymphocyte selection and immune tolerance. Immunol Res. 2002;26(1–3):255–263. doi:10.1385/IR:26:1-3:255
   PubMed Web of Science ®Google Scholar
• Mageed RA, Garaud S, Taher TE, et al. CD5 expression promotes multiple intracellular signaling pathways in B lymphocyte. Autoimmun Rev. 2012;11(11):795–798. doi:10.1016/j.autrev.2012.02.007
   PubMed Web of Science ®Google Scholar
• Turk V, Stoka V, Vasiljeva O, et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim Biophys Acta. 2012;1824(1):68–88. doi:10.1016/j.bbapap.2011.10.002
   PubMed Web of Science ®Google Scholar
• Hill LJ, Di Pietro V, Hazeldine J, et al. Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury. Sci Rep. 2017;7(1):5002. doi:10.1038/s41598-017-04722-5
   PubMedGoogle Scholar
• Ferrer-Mayorga G, Alvarez-Díaz S, Valle N, et al. Cystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expression. J Biol Chem. 2015;290(44):26533–26548. doi:10.1074/jbc.M115.660175
   PubMed Web of Science ®Google Scholar
• Hou Y, Wang Y, Chen J, Chen C. Dual Roles of Tumor Necrosis Factor Superfamily 14 in Antiviral Immunity. Viral Immunol. 2022;35(9):579–585. doi:10.1089/vim.2022.0070
   PubMed Web of Science ®Google Scholar
• Qu HQ, Snyder J, Connolly J, et al. Circulating LIGHT (TNFSF14) and Interleukin-18 Levels in Sepsis-Induced Multi-Organ Injuries. Biomedicines. 2022;10(2)264. doi:10.3390/biomedicines10020264
   PubMed Web of Science ®Google Scholar
• von Karstedt S, Montinaro A, Walczak H. Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy. Nat Rev Cancer. 2017;17(6):352–366. doi:10.1038/nrc.2017.28
   PubMed Web of Science ®Google Scholar
• Kiechl S, Schett G, Wenning G, et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation. 2004;109(18):2175–2180. doi:10.1161/01.CIR.0000127957.43874.BB
   PubMed Web of Science ®Google Scholar
• Vik A, Mathiesen EB, Brox J, et al. Serum osteoprotegerin is a predictor for incident cardiovascular disease and mortality in a general population: the Tromsø Study. J Thromb Haemost. 2011;9(4):638–644. doi:10.1111/j.1538-7836.2011.04222.x
   PubMed Web of Science ®Google Scholar