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Genome-wide SNP-Based Linkage Scan Identifies a Locus on 8q24 for an Age-Related Hearing Impairment Trait

Department of Medical Genetics, University of Antwerp, B-2610 Antwerp, Belgium.
The American Journal of Human Genetics (Impact Factor: 10.99). 09/2008; 83(3):401-7. DOI: 10.1016/j.ajhg.2008.08.002
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ABSTRACT Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.

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Available from: Elina Mäki-Torkko, Aug 27, 2015
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    • "In one study, about 40 different candidate genes were tested based on their association with Mendelian forms of hearing loss; the most significant association was within an intron of the grainyhead-like 2 gene (GRHL2, OMIM ID: 608576) (Van Laer et al., 2008). Several linkage studies were attempted, but they either failed to identify any genome-wide significant peaks or exhibited such broad peaks that it was impossible to identify specific causative genes or mutations (DeStefano et al., 2003; Garringer et al., 2006; Huyghe et al., 2008). A 500K-single nucleotide polymorphism (SNP) genome-wide association study of a large European cohort of older adults (Study 1) resulted in the identification of one haplotype within the glutamate metabotrophic receptor 7 (GRM7, OMIM ID: 604101) as harboring a significant risk allele for ARHI (Friedman et al., 2009). "
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