Abstract
Purpose
Obstructive sleep apnea (OSA) is the most common pathologic sleep disorder with an estimated prevalence in the USA of up to 25% of adult males. With military aviation being heavily comprised of adult men, the impact of OSA on flying operations is concerning as OSA is disqualifying for all flying classes in the US Air Force. In order to minimize the impact of OSA on operations, early identification of at-risk patients is critical in disease management. Individuals could be identified for whom regular polysomnography testing may reveal OSA while mild or sub-clinical, at which point treatment may be initiated in order to promote continued medical qualification for duty and career retention.
Methods
We performed a keyword search of PubMed, EMBASE, and Google Scholar along with searches in the NHGRI/EBI GWAS Catalogue and the Atlas of GWAS Summary Statistics. We included primary research from candidate gene, GWAS, and meta-analyses. We also included other review articles in our search to confirm interpretations and implications of any genetic associations with OSA. Only studies related to OSA susceptibility or risk were included.
Results
We identified 134 publications reporting or reviewing genetic associations with OSA risk. These papers reported 301 variants, of which 195 were unique and 33 were replicated in at least two papers. With respect to the strength of association, 43 variants exhibited odds ratios greater than 2. Finally, there were 84 null results reported, 51 of which were in conflict with reported associations.
Conclusion
There is ample evidence in the literature to confirm that genetics provide an important contribution to OSA development. The high number of strongly associated variants suggests that a polygenic risk model could be created with high predictive value for prognostic screening.
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Availability of data and materials
No primary data were collected in this review.
References
Barthel SW, Strome M (1999) Snoring, obstructive sleep apnea, and surgery. Med Clin N Am 83:85–96
Flemons WW (2002) Obstructive Sleep Apnea. N Engl J Med 347(7):498–504
Peppard PE, Young T, Barnet JH et al (2013) Increased prevalence of sleep-disordered breathing in adult. Am J Epidemiol 177(9):1006–1014
Mysliwiec V, Gill J, Lee H et al (2013) Sleep disorders in the US military personnel: a high rate of comorbid insomnia and obstructive sleep apnea. Chest 144(2):549–557
Ho ML, Brass SD (2011) Obstructive sleep apnea. Neurology Intl 3(e15):60–67
Chung F, Yegneswaran B, Liao P et al (2008) STOP Questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology 108(5):812–821
Levy P, Pepin JL, Mayer P et al (1996) Management of simple snoring, upper airway resistance syndrome, and moderate sleep apnea syndrome. Sleep 19(9):S101–S110
Chobanian AV, Bakris GL, Black HR et al (2003) Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 42:1206–52
Sjöström C, Lindberg E, Elmasry A et al (2002) Prevalence of sleep apnoea and snoring in hypertensive men: a population based study. Thorax 57:602–607
Logan AG, Perlikowski SM, Mente A et al (2001) High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertension 19:2271–2277
Drager LF, Bortolotto LA, Figueiredo AC et al (2007) Obstructive sleep apnea, hypertension and their interaction on arterial stiffness and heart remodeling. Chest 131:1379–1386
Drager LF, Bortolotto LA, Krieger EM, Lorenzi-Filho G (2009) Additive effects of obstructive sleep apnea and hypertension on early markers of carotid atherosclerosis. Hypertension 53:64–69
Bradley TD, Floras JS (2009) Obstructive sleep apnoea and its cardiovascular consequences. Lancet 373:82–93
Mickelson SA, Rosenthal LD, Rock JP, Senior BA, Friduss ME (1994) Obstructive sleep apnea syndrome and acromegaly. Otolayngol Head Neck Surg 111(1) 25-30. https://doi.org/10.1177/019459989411100107
Parish JM (2013) Genetic and immunologic aspects of sleep and sleep disorders Chest 143 5 1489 1499 https://doi.org/10.1378/chest.12-1219. Erratum.In:Chest.2013Aug;144(2):721
de Lima FF, Mazzotti DR, Tufik S, Bittencourt L (2016) The role inflammatory response genes in obstructive sleep apnea syndrome: a review. Sleep Breath 20(1):331–338. https://doi.org/10.1007/s11325-015-1226-7
Gehrman PR, Keenan BT, Byrne EM, Pack AI (2015) Genetics of sleep disorders. Psychiatr Clin North Am 38(4):667–681. https://doi.org/10.1016/j.psc.2015.07.004
Kaparianos A, Sampsonas F, Karkoulias K, Spiropoulos K (2006) Obstructive sleep apnoea syndrome and genes. Neth J Med 64(8):280–289
Kent BD, Ryan S, McNicholas WT (2010) The genetics of obstructive sleep apnoea. Curr Opin Pulm Med 16(6):536–542. https://doi.org/10.1097/MCP.0b013e32833ef7fe
Mukherjee S, Saxena R, Palmer LJ (2018) The genetics of obstructive sleep apnoea. Respirology 23(1):18–27. https://doi.org/10.1111/resp.13212
Polotsky VY, O’Donnell CP (2007) Genomics of sleep-disordered breathing. Proc Am Thorac Soc 4(1):121–126. https://doi.org/10.1513/pats.200606-134JG
Riha RL, Diefenbach K, Jennum P, McNicholas WT (2008) Management committee, COST B26 action on sleep apnoea syndrome. Genetic aspects of hypertension and metabolic disease in the obstructive sleep apnoea-hypopnoea syndrome. Sleep Med Rev. 12(1):49–63. https://doi.org/10.1016/j.smrv.2007.08.004
Riha RL, Gislasson T, Diefenbach K (2009) The phenotype and genotype of adult obstructive sleep apnoea/hypopnoea syndrome. Eur Respir J 33(3):646–655. https://doi.org/10.1183/09031936.00151008
Tanizawa K, Chin K (2018) Genetic factors in sleep-disordered breathing. Respir Investig 56(2):111–119. https://doi.org/10.1016/j.resinv.2017.11.012
Redline S, Tishler PV (2000) The genetics of sleep apnea. Sleep Med Rev 4(6):583–602. https://doi.org/10.1053/smrv.2000.0120
Casale M, Pappacena M, Rinaldi V, Bressi F, Baptista P, Salvinelli F (2009) Obstructive sleep apnea syndrome: from phenotype to genetic basis. Curr Genom 10 (2) 119-126. https://doi.org/10.2174/138920209787846998
Redline S, Tosteson T, Tishler PV, Carskadon MA, Millman RP (1992) Studies in the genetics of obstructive sleep apnea. Familial aggregation of symptoms associated with sleep-related breathing disturbances. Am Rev Respir Dis. 145(2 Pt 1):440–4. https://doi.org/10.1164/ajrccm/145.2_Pt_1.440 (Erratum in: Am Rev Respir Dis 1992 Apr;145(4 Pt 1):979. Milliman RP [corrected to Millman RP]. PMID: 1736754)
Varvarigou V, Dahabreh IJ, Malhotra A, Kales SN (2011) A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis. Sleep 34(11):1461–1468. https://doi.org/10.5665/sleep.1376
Kripke DF, Kline LE, Nievergelt CM, Murray SS, Shadan FF, Dawson A, Poceta JS, Cronin J, Jamil SM, Tranah GJ, Loving RT, Grizas AP, Hahn EK (2015) Genetic variants associated with sleep disorders. Sleep Med 16(2):217–224. https://doi.org/10.1016/j.sleep.2014.11.003
Zhang D, Xiao Y, Luo J (2014) Genetics of obstructive sleep apnea/hypopnea syndrome. Chin Med J (Engl) 127(17):3135–3141
Tan HL, Kheirandish-Gozal L, Gozal D (2014) The promise of translational and personalised approaches for paediatric obstructive sleep apnoea: an “Omics” perspective. Thorax 69(5):474–480. https://doi.org/10.1136/thoraxjnl-2013-204640
Moher D, Liberati A, Tetzlaff J, Altman D, the PRIMSA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. https://doi.org/10.1136/bjm.b2535
Buniello A, et al (2019) The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Research 47 (Database issue): D1005-D1012.
Watanabe K et al (2019) A global overview of pleiotropy and genetic architecture in complex traits. Nat Genet 51:1339–1348
Garvey JF, Pengo MF, Drakatos P, Kent BD (2015) Epidemiological aspects of obstructive sleep apnea. J Thorac Dis 7(5):920–929
Davies HTO, Crombie IK, Tavakoli M (1998) When can odds ratios mislead? BMJ 316(7136):989–991
Council on Foreign Relations. Demographics of the US Military. 13 July 2020. Available from https://www.cfr.org/backgrounder/demographics-us-military, Accessed 06 Apr 2021.
Caldwell JA, Knapik JJ, Lieberman HR (2017) Trends and factors associated with insomnia and sleep apnea in all United States military service members from 2005 to 2014. J Sleep Res 26:665–670
Duquette A, Dorr L (2015) Fact Sheet – Obstructive sleep apnea in aviation. Federal Aviation Administration. Available from: https://www.faa.gov/news/fact_sheets/news_story.cfm?newsId=18156; Accessed Mar 2, 2021
Atwood CW, Strollo Jr PJ, Givelber R (2011) Medical therapy for obstructive sleep apnea. Ch. 106 in principles and practice of sleep medicine, 5th ed. Edited by Kryger MH, Roth T, Dement WC. Saunders
Acknowledgements
The authors would like to thank the staff of the US Air Force School of Aerospace Medicine’s Franzello Aeromedical Library and Kristen Young and Elizabeth Beidelschies, in particular, for their assistance with gathering literature.
Funding
This work was funded internally by the US Air Force School of Aerospace Medicine. The views expressed are solely those of the authors and do not reflect the official policy or position of the US Air Force, the Department of Defense, or the US Government.
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Richard Chapleau conceived the idea, secured funding, performed the literature search, and wrote the genetics sections. Dara Regn edited the draft and wrote the sections related to aerospace medicine, pulmonology, and sleep medicine. Both authors edited and approved the final version.
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Chapleau, R.R., Regn, D.D. Integrating the precision, sleep, and aerospace medicine fields: a systematic review of the genetic predisposition for obstructive sleep apnea in military aviation. Sleep Breath 26, 505–512 (2022). https://doi.org/10.1007/s11325-021-02427-8
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DOI: https://doi.org/10.1007/s11325-021-02427-8