Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait

J.R. Huyghe, L. Van Laer, J.J. Hendrickx, E. Fransen, K. Demeester, V. Topsakal, S. Kunst, M. Manninen, M. Jensen, A. Bonaconsa, M. Mazzoli, M. Baur, S. Hannula, E. Maki-Torkko, A. Espeso, E. Van Eyken, A. Flaquer, C. Becker, D. Stephens, M. SorriE. Orzan, M. Bille, A. Parving, I. Pyykko, C.W.R.J. Cremers, H. Kremer, P.H. Van de Heyning, T.E. Wienker, P. Nurnberg, M. Pfister, G. Van Camp

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44 Citationer (Scopus)

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
Udgivelsesdato: 2008/9/12
OriginalsprogEngelsk
TidsskriftAmerican Journal of Human Genetics
Vol/bind83
Udgave nummer3
Sider (fra-til)401-407
Antal sider6
ISSN0002-9297
StatusUdgivet - 2008

Bibliografisk note

Times Cited: 0ArticleEnglishVan Camp, GUniv Antwerp, Dept Med Genet, B-2610 Antwerp, BelgiumCited References Count: 32349TWCELL PRESS600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USACAMBRIDGE

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