Genetic Contributors to Otitis Media: Agnostic Discovery Approaches

  • E. Kaitlynn Allen
  • Ani Manichaikul
  • Michèle M. Sale
Part of the following topical collections:
  1. Topical Collection on Otitis


Otitis media (OM) is the most common disease in children in the United States, with about $5 billion spent each year in direct and indirect costs. OM is the number one reason for pediatric antibiotic usage and surgery, although treatment options are limited. Numerous studies have established the high heritability of OM and a genetic contribution to OM pathogenesis. Candidate gene studies have highlighted the roles of inflammation, mucin secretion, and pathogen recognition, but this approach is unable to identify novel pathways to target for treatment or screening purposes. Here, we review the current literature on agnostic approaches to discover novel genes and pathways involved in OM pathogenesis.


Otitis media Discovery Genome Candidate genes Population studies Genetics 


Compliance with Ethics Guidelines

Conflict of Interest

Ani Manichaikul has received grant support from the Hearing Health Foundation.

E. Kaitlynn Allen and Michèle M. Sale declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. With regard to the authors’ research cited in this paper, all procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.


  1. 1.
    Gates GA. Cost-effectiveness considerations in otitis media treatment. Otolaryngol Head Neck Surg. 1996;114(4):525–30. doi: 10.1016/s0194-5998(96)70243-7.PubMedCrossRefGoogle Scholar
  2. 2.
    Gould JM, Matz PS. Otitis media. Pediatr Rev Am Acad Pediatr. 2010;31(3):102–16. doi: 10.1542/pir.31-3-102.CrossRefGoogle Scholar
  3. 3.
    Daly KA, Hoffman HJ, Kvaerner KJ, Kvestad E, Casselbrant ML, Homoe P, et al. Epidemiology, natural history, and risk factors: panel report from the Ninth International Research Conference on Otitis Media. Int J Pediatr Otorhinolaryngol. 2010;74(3):231–40. doi: 10.1016/j.ijporl.2009.09.006.PubMedCrossRefGoogle Scholar
  4. 4.
    Auinger P, Lanphear BP, Kalkwarf HJ, Mansour ME. Trends in otitis media among children in the United States. Pediatrics. 2003;112(3 Pt 1):514–20.PubMedCrossRefGoogle Scholar
  5. 5.
    Kvaerner KJ, Tambs K, Harris JR, Magnus P. Distribution and heritability of recurrent ear infections. Ann Otol Rhinol Laryngol. 1997;106(8):624–32.PubMedGoogle Scholar
  6. 6.
    Casselbrant ML, Mandel EM, Fall PA, Rockette HE, Kurs-Lasky M, Bluestone CD, et al. The heritability of otitis media: a twin and triplet study. JAMA : J Am Med Assoc. 1999;282(22):2125–30.CrossRefGoogle Scholar
  7. 7.
    Rovers M, Haggard M, Gannon M, Koeppen-Schomerus G, Plomin R. Heritability of symptom domains in otitis media: a longitudinal study of 1,373 twin pairs. Am J Epidemiol. 2002;155(10):958–64.PubMedCrossRefGoogle Scholar
  8. 8.
    Hafren L, Kentala E, Jarvinen TM, Leinonen E, Onkamo P, Kere J, et al. Genetic background and the risk of otitis media. Int J Pediatr Otorhinolaryngol. 2012;76(1):41–4. doi: 10.1016/j.ijporl.2011.09.026.PubMedCrossRefGoogle Scholar
  9. 9.
    Rye MS, Bhutta MF, Cheeseman MT, Burgner D, Blackwell JM, Brown SD, et al. Unraveling the genetics of otitis media: from mouse to human and back again. Mamm Genome: Off J Int Mamm Genome Soc. 2011;22(1–2):66–82. doi: 10.1007/s00335-010-9295-1.CrossRefGoogle Scholar
  10. 10.
    Macarthur CJ, Wilmot B, Wang L, Schuller M, Lighthall J, Trune D. Genetic susceptibility to chronic otitis media with effusion: Candidate gene SNPs. Laryngoscope. 2013. doi: 10.1002/lary.24349.PubMedGoogle Scholar
  11. 11.
    Bowden DW, An SS, Palmer ND, Brown WM, Norris JM, Haffner SM, et al. Molecular basis of a linkage peak: exome sequencing and family-based analysis identify a rare genetic variant in the ADIPOQ gene in the IRAS Family Study. Hum Mol Genet. 2010;19(20):4112–20. doi: 10.1093/hmg/ddq327.PubMedCrossRefGoogle Scholar
  12. 12.
    Fearnhead NS, Wilding JL, Winney B, Tonks S, Bartlett S, Bicknell DC, et al. Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas. Proc Natl Acad Sci U S A. 2004;101(45):15992–7. doi: 10.1073/pnas.0407187101.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Daly KA, Brown WM, Segade F, Bowden DW, Keats BJ, Lindgren BR, et al. Chronic and recurrent otitis media: a genome scan for susceptibility loci. Am J Hum Genet. 2004;75(6):988–97. doi: 10.1086/426061.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Chen WM, Allen EK, Mychaleckyj JC, Chen F, Hou X, Rich SS, et al. Significant linkage at chromosome 19q for otitis media with effusion and/or recurrent otitis media (COME/ROM). BMC Med Genet. 2011;12:124. doi: 10.1186/1471-2350-12-124.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Jiao K, Zhou Y, Hogan BL. Identification of mZnf8, a mouse Kruppel-like transcriptional repressor, as a novel nuclear interaction partner of Smad1. Mol Cell Biol. 2002;22(21):7633–44.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821–32. doi: 10.1016/j.cell.2010.01.040.PubMedCrossRefGoogle Scholar
  17. 17.
    Taxman DJ, Huang MT, Ting JP. Inflammasome inhibition as a pathogenic stealth mechanism. Cell Host Microbe. 2010;8(1):7–11. doi: 10.1016/j.chom.2010.06.005.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Kanneganti TD. Central roles of NLRs and inflammasomes in viral infection. Nat Reviewsimmunol. 2010. doi: 10.1038/nri2851.Google Scholar
  19. 19.
    Valletta EA, Rigo A, Bonazzi L, Zanolla L, Mastella G. Modification of some markers of inflammation during treatment for acute respiratory exacerbation in cystic fibrosis. Acta Paediatr (Oslo, Norway : 1992). 1992;81(3):227–30.CrossRefGoogle Scholar
  20. 20.
    Casselbrant ML, Mandel EM, Jung J, Ferrell RE, Tekely K, Szatkiewicz JP, et al. Otitis media: a genome-wide linkage scan with evidence of susceptibility loci within the 17q12 and 10q22.3 regions. BMC Med Genet. 2009;10:85. doi: 10.1186/1471-2350-10-85.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Rye MS, Warrington NM, Scaman ESH, Vijayasekaran S, Coates HL, Anderson D, et al. Genome-Wide Association Study to Identify the Genetic Determinants of Otitis Media Susceptibility in Childhood. PloS One. 2012;7(10):e48215. doi: 10.1371/journal.pone.0048215.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Allen EK, Chen WM, Weeks DE, Chen F, Hou X, Mattos JL, et al. A Genome-Wide Association Study of Chronic Otitis Media with Effusion and Recurrent Otitis Media Identifies a Novel Susceptibility Locus on Chromosome 2. J Assoc Res Otolaryngol: JARO. 2013. doi: 10.1007/s10162-013-0411-2.PubMedGoogle Scholar
  23. 23.
    Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56–65. doi: 10.1038/nature11632.PubMedCrossRefGoogle Scholar
  24. 24.
    Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, et al. Integrating common and rare genetic variation in diverse human populations. Nature. 2010;467(7311):52–8. doi: 10.1038/nature09298.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • E. Kaitlynn Allen
    • 1
    • 2
  • Ani Manichaikul
    • 1
    • 3
  • Michèle M. Sale
    • 1
    • 2
    • 4
  1. 1.Center for Public Health GenomicsUniversity of VirginiaCharlottesvilleUSA
  2. 2.Department of Biochemistry and Molecular GeneticsUniversity of VirginiaCharlottesvilleUSA
  3. 3.Department of Public Health Sciences, Division of Biostatistics and EpidemiologyUniversity of VirginiaCharlottesvilleUSA
  4. 4.Department of MedicineUniversity of VirginiaCharlottesvilleUSA

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