title: Genome-wide association study for age-related hearing loss (AHL) in the mouse: a meta-analysis.
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.
authors.affiliation: Department of Cell and Molecular Biology and Genetics, House Research Institute, Los Angeles, CA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ohmen
authors.forename: Eun Yong
authors.initials: EY
authors.lastname: Kang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Jong Wha
authors.initials: JW
authors.lastname: Joo
authors.forename: Farhad
authors.initials: F
authors.lastname: Hormozdiari
authors.forename: Qing Yin
authors.initials: QY
authors.lastname: Zheng
authors.forename: Richard C
authors.initials: RC
authors.lastname: Davis
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Eleazar
authors.initials: E
authors.lastname: Eskin
authors.forename: Rick A
authors.initials: RA
authors.lastname: Friedman
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D055106:Genome-Wide Association Study; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D011336:Probability; D040641:Quantitative Trait Loci