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

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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.

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Acknowledgments

J.O., X.L., and R.F. are supported by the National Institutes of Health grants NIDCD R01DC010856-01. E.Y.K., J.W.J, F.H., and E.E. are supported by the National Science Foundation grants 0513612, 0731455, 0729049, 0916676, and 1065276, and the National Institutes of Health grants K25-HL080079, U01-DA024417, P01-HL30568, and PO1-HL28481. Q.Y.Z is supported by the US National Institutes of Health grants NIDCD R01DC009246.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology and Genetics, House Research Institute, Los Angeles, CA, USA

    Jeffrey Ohmen, Xin Li & Rick A. Friedman

  2. Department of Computer Science, University of California, Los Angeles, Los Angeles, CA, USA

    Eun Yong Kang, Farhad Hormozdiari & Eleazar Eskin

  3. Interdepartmental Program in Bioinformatics, University of California, Los Angeles, Los Angeles, CA, USA

    Jong Wha Joo

  4. Department of Otolaryngology, Case Western Reserve University, Cleveland, OH, USA

    Qing Yin Zheng

  5. Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

    Richard C. Davis & Aldons J. Lusis

  6. Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA

    Aldons J. Lusis & Eleazar Eskin

  7. Department of Otolaryngology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Rick A. Friedman

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  1. Jeffrey Ohmen
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  2. Eun Yong Kang
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  9. Eleazar Eskin
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  10. Rick A. Friedman
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Correspondence to Rick A. Friedman.

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Jeffrey Ohmen and Eun Yong Kang contributed equally to this work.

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Ohmen, J., Kang, E.Y., Li, X. et al. Genome-Wide Association Study for Age-Related Hearing Loss (AHL) in the Mouse: A Meta-Analysis. JARO 15, 335–352 (2014). https://doi.org/10.1007/s10162-014-0443-2

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