| Literature DB >> 18760390 |
Jeroen R Huyghe1, Lut Van Laer, Jan-Jaap Hendrickx, Erik Fransen, Kelly Demeester, Vedat Topsakal, Sylvia Kunst, Minna Manninen, Mona Jensen, Amanda Bonaconsa, Manuela Mazzoli, Manuela Baur, Samuli Hannula, Elina Mäki-Torkko, Angeles Espeso, Els Van Eyken, Antonia Flaquer, Christian Becker, Dafydd Stephens, Martti Sorri, Eva Orzan, Michael Bille, Agnete Parving, Ilmari Pyykkö, Cor W R J Cremers, Hannie Kremer, Paul H Van de Heyning, Thomas F Wienker, Peter Nürnberg, Markus Pfister, Guy Van Camp.
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.Entities:
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Year: 2008 PMID： 18760390 PMCID： PMC2556434 DOI： 10.1016/j.ajhg.2008.08.002
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025