The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment

Lut Van Laer, Els Van Eyken, Erik Fransen, Jeroen R. Huyghe, Vedat Topsakal, Jan Jaap Hendrickx, Samuli Hannula, Elina Mäki-Torkko, Mona Jensen, Kelly Demeester, Manuela Baur, Amanda Bonaconsa, Manuela Mazzoli, Angeles Espeso, Katia Verbruggen, Joke Huyghe, Patrick Huygen, Sylvia Kunst, Minna Manninen, Annelies Konings & 15 others Amalia N. Diaz-Lacava, Michael Steffens, Thomas F. Wienker, Ilmari Pyykkö, Cor W R J Cremers, Hannie Kremer, Ingeborg Dhooge, Dafydd Stephens, Eva Orzan, Markus Pfister, Michael Bille, Agnete Parving, Martti Sorri, Paul H. Van de Heyning, Guy Van Camp

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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.

Original languageEnglish
Pages (from-to)159-169
Number of pages11
JournalHuman Molecular Genetics
Volume17
Issue number2
DOIs
Publication statusPublished - Jan 15 2008

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Hearing Loss
Single Nucleotide Polymorphism
Genes
Statistical Data Interpretation
Introns
Protein Isoforms

ASJC Scopus subject areas

  • Genetics

Cite this

Van Laer, L., Van Eyken, E., Fransen, E., Huyghe, J. R., Topsakal, V., Hendrickx, J. J., ... Van Camp, G. (2008). The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment. Human Molecular Genetics, 17(2), 159-169. https://doi.org/10.1093/hmg/ddm292

The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment. / Van Laer, Lut; Van Eyken, Els; Fransen, Erik; Huyghe, Jeroen R.; Topsakal, Vedat; Hendrickx, Jan Jaap; Hannula, Samuli; Mäki-Torkko, Elina; Jensen, Mona; Demeester, Kelly; Baur, Manuela; Bonaconsa, Amanda; Mazzoli, Manuela; Espeso, Angeles; Verbruggen, Katia; Huyghe, Joke; Huygen, Patrick; Kunst, Sylvia; Manninen, Minna; Konings, Annelies; Diaz-Lacava, Amalia N.; Steffens, Michael; Wienker, Thomas F.; Pyykkö, Ilmari; Cremers, Cor W R J; Kremer, Hannie; Dhooge, Ingeborg; Stephens, Dafydd; Orzan, Eva; Pfister, Markus; Bille, Michael; Parving, Agnete; Sorri, Martti; Van de Heyning, Paul H.; Van Camp, Guy.

In: Human Molecular Genetics, Vol. 17, No. 2, 15.01.2008, p. 159-169.

Research output: Contribution to journalArticle

Van Laer, L, Van Eyken, E, Fransen, E, Huyghe, JR, Topsakal, V, Hendrickx, JJ, Hannula, S, Mäki-Torkko, E, Jensen, M, Demeester, K, Baur, M, Bonaconsa, A, Mazzoli, M, Espeso, A, Verbruggen, K, Huyghe, J, Huygen, P, Kunst, S, Manninen, M, Konings, A, Diaz-Lacava, AN, Steffens, M, Wienker, TF, Pyykkö, I, Cremers, CWRJ, Kremer, H, Dhooge, I, Stephens, D, Orzan, E, Pfister, M, Bille, M, Parving, A, Sorri, M, Van de Heyning, PH & Van Camp, G 2008, 'The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment', Human Molecular Genetics, vol. 17, no. 2, pp. 159-169. https://doi.org/10.1093/hmg/ddm292
Van Laer L, Van Eyken E, Fransen E, Huyghe JR, Topsakal V, Hendrickx JJ et al. The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment. Human Molecular Genetics. 2008 Jan 15;17(2):159-169. https://doi.org/10.1093/hmg/ddm292
Van Laer, Lut ; Van Eyken, Els ; Fransen, Erik ; Huyghe, Jeroen R. ; Topsakal, Vedat ; Hendrickx, Jan Jaap ; Hannula, Samuli ; Mäki-Torkko, Elina ; Jensen, Mona ; Demeester, Kelly ; Baur, Manuela ; Bonaconsa, Amanda ; Mazzoli, Manuela ; Espeso, Angeles ; Verbruggen, Katia ; Huyghe, Joke ; Huygen, Patrick ; Kunst, Sylvia ; Manninen, Minna ; Konings, Annelies ; Diaz-Lacava, Amalia N. ; Steffens, Michael ; Wienker, Thomas F. ; Pyykkö, Ilmari ; Cremers, Cor W R J ; Kremer, Hannie ; Dhooge, Ingeborg ; Stephens, Dafydd ; Orzan, Eva ; Pfister, Markus ; Bille, Michael ; Parving, Agnete ; Sorri, Martti ; Van de Heyning, Paul H. ; Van Camp, Guy. / The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment. In: Human Molecular Genetics. 2008 ; Vol. 17, No. 2. pp. 159-169.
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AU - Fransen, Erik

AU - Huyghe, Jeroen R.

AU - Topsakal, Vedat

AU - Hendrickx, Jan Jaap

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AU - Jensen, Mona

AU - Demeester, Kelly

AU - Baur, Manuela

AU - Bonaconsa, Amanda

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AU - Espeso, Angeles

AU - Verbruggen, Katia

AU - Huyghe, Joke

AU - Huygen, Patrick

AU - Kunst, Sylvia

AU - Manninen, Minna

AU - Konings, Annelies

AU - Diaz-Lacava, Amalia N.

AU - Steffens, Michael

AU - Wienker, Thomas F.

AU - Pyykkö, Ilmari

AU - Cremers, Cor W R J

AU - Kremer, Hannie

AU - Dhooge, Ingeborg

AU - Stephens, Dafydd

AU - Orzan, Eva

AU - Pfister, Markus

AU - Bille, Michael

AU - Parving, Agnete

AU - Sorri, Martti

AU - Van de Heyning, Paul H.

AU - Van Camp, Guy

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