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