Abstract
Obstructive sleep apnea (OSA) is a highly prevalent disease with severe effects on health. Nevertheless, nowadays, we lack biomarkers for OSA diagnosis that provide information about treatment outcomes, complications, and comorbidities. OSA is a very complex trait from the clinical and genetic points of view. It is conditioned by a plethora of low-risk genes, their interactions, and their interplay with a network of environmental factors. This chapter aims to be a review of the different genetic biomarkers of OSA as well as the different types of study designs for their identification, namely linkage analyses, genome-wide association studies (GWAS), candidate gene association studies, and whole-genome or -exome sequencing by next-generation sequencing (NGS).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Ovchinsky A, Rao M, Lotwin I, Goldstein NA. The familial aggregation of pediatric obstructive sleep apnea syndrome. Arch Otolaryngol Head Neck Surg. 2002;128:815–8. https://doi.org/10.1001/archotol.128.7.815.
Redline S, Tishler PV. The genetics of sleep apnea. Sleep Med Rev. 2000;4:583–602. https://doi.org/10.1053/smrv.2000.0120.
Mukherjee S, Saxena R, Palmer LJ. The genetics of obstructive sleep apnoea. Respirology. 2018;23:18–27. https://doi.org/10.1111/resp.13212.
Palmer LJ, Buxbaum SG, Larkin E, Patel SR, Elston RC, Tishler PV, Redline S. Whole-genome scan for obstructive sleep apnea and obesity. Am J Hum Genet. 2003;72:340–50. https://doi.org/10.1164/rccm.200304-493OC.
McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, Hirschhorn JN. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet. 2008;9:356–69. https://doi.org/10.1038/nrg2344.
GWAS Catalogue. https://www.ebi.ac.uk/gwas/. Accessed 2 April 2022; n.d..
Cade BE, Chen H, Stilp AM, Gleason KJ, Sofer T, Ancoli-Israel S, et al. Genetic associations with obstructive sleep apnea traits in Hispanic/Latino Americans. Am J Respir Crit Care Med. 2016;194:886–97. https://doi.org/10.1164/rccm.201512-2431OC.
FinnGen Project. https://www.finngen.fi/en. Accessed 2 April 2022; n.d..
Strausz S, Ruotsalainen S, Ollila HM, Karjalainen J, Kiiskinen T, Reeve M, et al. Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health. Eur Respir J. 2021;57:2003091. https://doi.org/10.1183/13993003.03091-2020.
Baik I, Seo HS, Yoon D, Kim SH, Shin C. Associations of sleep apnea, NRG1 polymorphisms, alcohol consumption, and cerebral white matter hyperintensities: analysis with genome-wide association data. Sleep. 2015;38:1137–43. https://doi.org/10.5665/sleep.4830.
Parish JM. Genetic and immunologic aspects of sleep and sleep disorders. Chest. 2013;143:1489–99. https://doi.org/10.1378/chest.12-1219.
Qin B, Sun Z, Liang Y, Yang Z, Zhong R. The association of 5-HT2A, 5-HTT, and LEPR polymorphisms with obstructive sleep apnea syndrome: a systematic review and meta-analysis. PLoS One. 2014;9:e95856. https://doi.org/10.1371/journal.pone.0095856.
Parsons MJ. On the genetics of sleep disorders: genome-wide association studies and beyond. Adv Genom Genet. 2015;5:293–303. https://doi.org/10.2147/AGG.S57139.
Patel SR, Goodloe R, De G, Kowgier M, Weng J, Buxbaum SG, et al. Association of genetic loci with sleep apnea in European Americans and African-Americans. PLoS One. 2012;7:e48836. https://doi.org/10.1371/journal.pone.0048836.
van der Spek A, Luik AI, Kocevska D, Liu C, Brouwer RWW, van Rooij JGJ, et al. Exome-wide meta-analysis identifies rare 3'-UTR variant in ERCC1/CD3EAP associated with symptoms of sleep apnea. Front Genet. 2017;8:151. https://doi.org/10.3389/fgene.2017.00151.
Gehrman PR, Keenan BT, Byrne EM, Pack AI. Genetics of sleep disorders. Psychiatr Clin North Am. 2015;38:667–81. https://doi.org/10.1016/j.psc.2015.07.004.
Zinchuk AV, Gentry MJ, Concato J, Yaggi HK. Phenotypes in obstructive sleep apnea: a definition, examples and evolution of approaches. Sleep Med Rev. 2017;35:113e123. https://doi.org/10.1016/j.smrv.2016.10.002.
Li HY, Tsai MS, Huang CG, Wang RYL, Chuang LP, Chen NH, Liu CH, Hsu CM, Cheng WN, Lee LA. Alterations in Alzheimer's disease-associated gene expression in severe obstructive sleep apnea patients. J Clin Med. 2019;8(9):1361. https://doi.org/10.3390/jcm8091361.
Chen YC, Chen KD, Su MC, Chin CH, Chen CJ, Liou CW, et al. Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea. PLoS One. 2017;12:e0176575. https://doi.org/10.1371/journal.pone.0176575.
Khurana S, Sharda S, Saha B, Kumar S, Guleria R, Bose S. Canvassing the aetiology, prognosis and molecular signatures of obstructive sleep apnoea. Biomarkers. 2019;24:1–16. https://doi.org/10.1080/1354750X.2018.1514655.
Chen YC, Chen TW, Su MC, Chen CJ, Chen KD, Liou CW, et al. Whole genome DNA methylation analysis of obstructive sleep apnea: IL1R2, NPR2, AR, SP140 methylation and clinical phenotype. Sleep. 2016;39:743–55. https://doi.org/10.5665/sleep.5620.
Kim J, Bhattacharjee R, Khalyfa A, Kheirandish-Gozal L, Capdevila OS, Wang Y, Gozal D. DNA methylation in inflammatory genes among children with obstructive sleep apnea. Am J Respir Crit Care Med. 2012;185:330–8. https://doi.org/10.1164/rccm.201106-1026OC.
Ambati A, Ju YE, Lin L, Olesen AN, Koch H, Hedou JJ, et al. Proteomic biomarkers of sleep apnea. Sleep. 2020;43:zsaa086. https://doi.org/10.1093/sleep/zsaa086.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Patiño-García, A. (2023). Genetics of Obstructive Sleep Apnea. In: Baptista, P.M., Lugo Saldaña, R., Amado, S. (eds) Obstructive Sleep Apnea. Springer, Cham. https://doi.org/10.1007/978-3-031-35225-6_28
Download citation
DOI: https://doi.org/10.1007/978-3-031-35225-6_28
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-35224-9
Online ISBN: 978-3-031-35225-6
eBook Packages: MedicineMedicine (R0)