Genome-Wide Association Study for Age-Related Hearing Loss (AHL) in the Mouse: A Meta-Analysis

  • Jeffrey Ohmen
  • Eun Yong Kang
  • Xin Li
  • Jong Wha Joo
  • Farhad Hormozdiari
  • Qing Yin Zheng
  • Richard C. Davis
  • Aldons J. Lusis
  • Eleazar Eskin
  • Rick A. Friedman
Research Article

Abstract

Age-related hearing loss (AHL) is characterized by a symmetric sensorineural hearing loss primarily in high frequencies and individuals have different levels of susceptibility to AHL. Heritability studies have shown that the sources of this variance are both genetic and environmental, with approximately half of the variance attributable to hereditary factors as reported by Huag and Tang (Eur Arch Otorhinolaryngol 267(8):1179–1191, 2010). Only a limited number of large-scale association studies for AHL have been undertaken in humans, to date. An alternate and complementary approach to these human studies is through the use of mouse models. Advantages of mouse models include that the environment can be more carefully controlled, measurements can be replicated in genetically identical animals, and the proportion of the variability explained by genetic variation is increased. Complex traits in mouse strains have been shown to have higher heritability and genetic loci often have stronger effects on the trait compared to humans. Motivated by these advantages, we have performed the first genome-wide association study of its kind in the mouse by combining several data sets in a meta-analysis to identify loci associated with age-related hearing loss. We identified five genome-wide significant loci (<10−6). One of these loci confirmed a previously identified locus (ahl8) on distal chromosome 11 and greatly narrowed the candidate region. Specifically, the most significant associated SNP is located 450 kb upstream of Fscn2. These data confirm the utility of this approach and provide new high-resolution mapping information about variation within the mouse genome associated with hearing loss.

Keywords

genome-wide association study age-related hearing loss (ARL) meta-analysis random-effects model mouse models 

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Copyright information

© Association for Research in Otolaryngology 2014

Authors and Affiliations

  • Jeffrey Ohmen
    • 1
  • Eun Yong Kang
    • 2
  • Xin Li
    • 1
  • Jong Wha Joo
    • 3
  • Farhad Hormozdiari
    • 2
  • Qing Yin Zheng
    • 4
  • Richard C. Davis
    • 5
  • Aldons J. Lusis
    • 5
    • 6
  • Eleazar Eskin
    • 2
    • 6
  • Rick A. Friedman
    • 1
    • 7
  1. 1.Department of Cell and Molecular Biology and GeneticsHouse Research InstituteLos AngelesUSA
  2. 2.Department of Computer ScienceUniversity of California, Los AngelesLos AngelesUSA
  3. 3.Interdepartmental Program in BioinformaticsUniversity of California, Los AngelesLos AngelesUSA
  4. 4.Department of OtolaryngologyCase Western Reserve UniversityClevelandUSA
  5. 5.Department of MedicineUniversity of California, Los AngelesLos AngelesUSA
  6. 6.Department of Human GeneticsUniversity of California, Los AngelesLos AngelesUSA
  7. 7.Department of Otolaryngology, Zilkha Neurogenetic Institute, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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