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

Jeroen R. Huyghe, 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 SorriEva 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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalAmerican Journal of Human Genetics
Volume83
Issue number3
DOIs
Publication statusPublished - Sep 12 2008

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ASJC Scopus subject areas

  • Genetics

Cite this

Huyghe, J. R., Van Laer, L., Hendrickx, J. J., Fransen, E., Demeester, K., Topsakal, V., Kunst, S., Manninen, M., Jensen, M., Bonaconsa, A., Mazzoli, M., Baur, M., Hannula, S., Mäki-Torkko, E., Espeso, A., Van Eyken, E., Flaquer, A., Becker, C., Stephens, D., ... Van Camp, G. (2008). Genome-wide SNP-Based Linkage Scan Identifies a Locus on 8q24 for an Age-Related Hearing Impairment Trait. American Journal of Human Genetics, 83(3), 401-407. https://doi.org/10.1016/j.ajhg.2008.08.002