title: The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment.
abstract: Age-related hearing impairment (ARHI) is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. The contribution of various environmental factors has been relatively extensively studied. In contrast, investigations to identify the genetic risk factors have only recently been initiated. In this paper we describe the results of an association study performed on 2418 ARHI samples derived from nine centers from seven European countries. In 70 candidate genes, a total of 768 tag single nucleotide polymorphisms (SNPs) were selected based on HAPMAP data. These genes were chosen among the monogenic hearing loss genes identified in mice and men in addition to several strong functional candidates. After genotyping and data polishing, statistical analysis of all samples combined resulted in a P-value that survived correction for multiple testing for one SNP in the GRHL2 gene. Other SNPs in this gene were also associated, albeit to a lesser degree. Subsequently, an analysis of the most significant GRHL2 SNP was performed separately for each center. The direction of the association was identical in all nine centers. Two centers showed significant associations and a third center showed a trend towards significance. Subsequent fine mapping of this locus demonstrated that the majority of the associated SNPs reside in intron 1. We hypothesize that the causative variant may change the expression levels of a GRHL2 isoform.
authors.affiliation: Department of Medical Genetics, University of Antwerp, B-2610 Antwerp, Belgium.
authors.forename: Lut
authors.initials: L
authors.lastname: Van Laer
authors.forename: Els
authors.initials: E
authors.lastname: Van Eyken
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.forename: Jeroen R
authors.initials: JR
authors.lastname: Huyghe
authors.forename: Vedat
authors.initials: V
authors.lastname: Topsakal
authors.forename: Jan-Jaap
authors.initials: JJ
authors.lastname: Hendrickx
authors.forename: Samuli
authors.initials: S
authors.lastname: Hannula
authors.forename: Elina
authors.initials: E
authors.lastname: Mäki-Torkko
authors.forename: Mona
authors.initials: M
authors.lastname: Jensen
authors.forename: Kelly
authors.initials: K
authors.lastname: Demeester
authors.forename: Manuela
authors.initials: M
authors.lastname: Baur
authors.forename: Amanda
authors.initials: A
authors.lastname: Bonaconsa
authors.forename: Manuela
authors.initials: M
authors.lastname: Mazzoli
authors.forename: Angeles
authors.initials: A
authors.lastname: Espeso
authors.forename: Katia
authors.initials: K
authors.lastname: Verbruggen
authors.forename: Joke
authors.initials: J
authors.lastname: Huyghe
authors.forename: Patrick
authors.initials: P
authors.lastname: Huygen
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kunst
authors.forename: Minna
authors.initials: M
authors.lastname: Manninen
authors.forename: Annelies
authors.initials: A
authors.lastname: Konings
authors.forename: Amalia N
authors.initials: AN
authors.lastname: Diaz-Lacava
authors.forename: Michael
authors.initials: M
authors.lastname: Steffens
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Ilmari
authors.initials: I
authors.lastname: Pyykkö
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Dhooge
authors.forename: Dafydd
authors.initials: D
authors.lastname: Stephens
authors.forename: Eva
authors.initials: E
authors.lastname: Orzan
authors.forename: Markus
authors.initials: M
authors.lastname: Pfister
authors.forename: Michael
authors.initials: M
authors.lastname: Bille
authors.forename: Agnete
authors.initials: A
authors.lastname: Parving
authors.forename: Martti
authors.initials: M
authors.lastname: Sorri
authors.forename: Paul H
authors.initials: PH
authors.lastname: Van de Heyning
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D005060:Europe; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011304:Presbycusis / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C470830:GRHL2 protein, human; D020033:Protein Isoforms; D014157:Transcription Factors