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Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait |
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| Authors: | Huyghe Jeroen R Van Laer Lut Hendrickx Jan-Jaap Fransen Erik Demeester Kelly Topsakal Vedat Kunst Sylvia Manninen Minna Jensen Mona Bonaconsa Amanda Mazzoli Manuela Baur Manuela Hannula Samuli Mäki-Torkko Elina Espeso Angeles Van Eyken Els Flaquer Antonia Becker Christian Stephens Dafydd Sorri Martti Orzan Eva Bille Michael Parving Agnete Pyykkö Ilmari Cremers Cor W R J Kremer Hannie Van de Heyning Paul H Wienker Thomas F Nürnberg Peter Pfister Markus Van Camp Guy |
| Institution: | 1 Department of Medical Genetics, University of Antwerp, B-2610 Antwerp, Belgium 2 Department of Otorhinolaryngology, University Hospital of Antwerp, B-2650 Antwerp, Belgium 3 Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, NL-6500 HB Nijmegen, the Netherlands 4 Department of Otorhinolaryngology, University of Tampere, FIN-33014 Tampere, Finland 5 Department of Audiology, Bispebjerg Hospital, DK-2400 Copenhagen, Denmark 6 Department of Oto-surgery, University Hospital Padova, I-35128 Padova, Italy 7 Department of Otorhinolaryngology, University of Tübingen, D-72074 Tübingen, Germany 8 Department of Otorhinolaryngology, University of Oulu, FIN-90220 Oulu, Finland 9 Welsh Hearing Institute, Cardiff University, Cardiff CF4 4XW, UK 10 Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, D-53105 Bonn, Germany 11 Cologne Center for Genomics (CCG) and Institute for Genetics, University of Cologne, D-50674 Cologne, Germany 12 Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, D-50674 Cologne, Germany 13 Nijmegen Centre for Molecular Life Sciences, NL-6500 HB Nijmegen, The Netherlands |
| 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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