title: Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait.
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.
authors.affiliation: Department of Medical Genetics, University of Antwerp, B-2610 Antwerp, Belgium.
authors.forename: Jeroen R
authors.initials: JR
authors.lastname: Huyghe
authors.forename: Lut
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authors.lastname: Van Laer
authors.forename: Jan-Jaap
authors.initials: JJ
authors.lastname: Hendrickx
authors.forename: Erik
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authors.lastname: Fransen
authors.forename: Kelly
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authors.lastname: Demeester
authors.forename: Vedat
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authors.lastname: Kunst
authors.forename: Minna
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authors.forename: Mona
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authors.lastname: Jensen
authors.forename: Amanda
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authors.lastname: Bonaconsa
authors.forename: Manuela
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authors.forename: Samuli
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authors.lastname: Hannula
authors.forename: Elina
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authors.lastname: Mäki-Torkko
authors.forename: Angeles
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authors.lastname: Espeso
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authors.forename: Antonia
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authors.lastname: Flaquer
authors.forename: Christian
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authors.forename: Dafydd
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authors.lastname: Stephens
authors.forename: Martti
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authors.forename: Eva
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authors.lastname: Orzan
authors.forename: Michael
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authors.lastname: Bille
authors.forename: Agnete
authors.initials: A
authors.lastname: Parving
authors.forename: Ilmari
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authors.lastname: Pyykkö
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
authors.forename: Hannie
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authors.lastname: Kremer
authors.forename: Paul H
authors.initials: PH
authors.lastname: Van de Heyning
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Markus
authors.initials: M
authors.lastname: Pfister
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp