GRM7 variants confer susceptibility to age-related hearing impairment

Rick A. Friedman, Lut Van Laer, Matthew J. Huentelman, Sonal S. Sheth, Els Van Eyken, Jason J. Corneveaux, Waibhav D. Tembe, Rebecca F. Halperin, Ashley Q. Thorburn, Sofie Thys, Sarah Bonneux, Erik Fransen, Jeroen Huyghe, Ilmari Pyykkö, Cor W R J Cremers, Hannie Kremer, Ingeborg Dhooge, Dafydd Stephens, Eva Orzan, Markus PfisterMichael Bille, Agnete Parving, Martti Sorri, Paul H. Van De Heyning, Linna Makmura, Jeffrey D. Ohmen, Frederick H. Linthicum, Jose N. Fayad, John V. Pearson, David W. Craig, Dietrich A. Stephan, Guy Van Camp

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Age-related hearing impairment (ARHI), or presbycusis, is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. Here we describe the results of the first whole genome association study for ARHI. The study was performed using 846 cases and 846 controls selected from 3434 individuals collected by eight centers in six European countries. DNA pools for cases and controls were allelotyped on the Affymetrix 500K GeneChip® for each center separately. The 252 top-ranked single nucleotide polymorphisms (SNPs) identified in a non-Finnish European sample group (1332 samples) and the 177 top-ranked SNPs from a Finnish sample group (360 samples) were confirmed using individual genotyping. Subsequently, the 23 most interesting SNPs were individually genotyped in an independent European replication group (138 samples). This resulted in the identification of a highly significant and replicated SNP located in GRM7, the gene encoding metabotropic glutamate receptor type 7. Also in the Finnish sample group, two GRM7 SNPs were significant, albeit in a different region of the gene. As the Finnish are genetically distinct from the rest of the European population, this may be due to allelic heterogeneity. We performed histochemical studies in human and mouse and showed that mGluR7 is expressed in hair cells and in spiral ganglion cells of the inner ear. Together these data indicate that common alleles of GRM7 contribute to an individual's risk of developing ARHI, possibly through a mechanism of altered susceptibility to glutamate excitotoxicity.

Original languageEnglish
Pages (from-to)785-796
Number of pages12
JournalHuman Molecular Genetics
Volume18
Issue number4
DOIs
Publication statusPublished - 2009

Fingerprint

Hearing Loss
Single Nucleotide Polymorphism
Presbycusis
Spiral Ganglion
Genome-Wide Association Study
Inner Ear
Genes
Glutamic Acid
Alleles
DNA
Population
metabotropic glutamate receptor 7

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Friedman, R. A., Van Laer, L., Huentelman, M. J., Sheth, S. S., Van Eyken, E., Corneveaux, J. J., ... Van Camp, G. (2009). GRM7 variants confer susceptibility to age-related hearing impairment. Human Molecular Genetics, 18(4), 785-796. https://doi.org/10.1093/hmg/ddn402

GRM7 variants confer susceptibility to age-related hearing impairment. / Friedman, Rick A.; Van Laer, Lut; Huentelman, Matthew J.; Sheth, Sonal S.; Van Eyken, Els; Corneveaux, Jason J.; Tembe, Waibhav D.; Halperin, Rebecca F.; Thorburn, Ashley Q.; Thys, Sofie; Bonneux, Sarah; Fransen, Erik; Huyghe, Jeroen; 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.; Makmura, Linna; Ohmen, Jeffrey D.; Linthicum, Frederick H.; Fayad, Jose N.; Pearson, John V.; Craig, David W.; Stephan, Dietrich A.; Van Camp, Guy.

In: Human Molecular Genetics, Vol. 18, No. 4, 2009, p. 785-796.

Research output: Contribution to journalArticle

Friedman, RA, Van Laer, L, Huentelman, MJ, Sheth, SS, Van Eyken, E, Corneveaux, JJ, Tembe, WD, Halperin, RF, Thorburn, AQ, Thys, S, Bonneux, S, Fransen, E, Huyghe, J, Pyykkö, I, Cremers, CWRJ, Kremer, H, Dhooge, I, Stephens, D, Orzan, E, Pfister, M, Bille, M, Parving, A, Sorri, M, Van De Heyning, PH, Makmura, L, Ohmen, JD, Linthicum, FH, Fayad, JN, Pearson, JV, Craig, DW, Stephan, DA & Van Camp, G 2009, 'GRM7 variants confer susceptibility to age-related hearing impairment', Human Molecular Genetics, vol. 18, no. 4, pp. 785-796. https://doi.org/10.1093/hmg/ddn402
Friedman RA, Van Laer L, Huentelman MJ, Sheth SS, Van Eyken E, Corneveaux JJ et al. GRM7 variants confer susceptibility to age-related hearing impairment. Human Molecular Genetics. 2009;18(4):785-796. https://doi.org/10.1093/hmg/ddn402
Friedman, Rick A. ; Van Laer, Lut ; Huentelman, Matthew J. ; Sheth, Sonal S. ; Van Eyken, Els ; Corneveaux, Jason J. ; Tembe, Waibhav D. ; Halperin, Rebecca F. ; Thorburn, Ashley Q. ; Thys, Sofie ; Bonneux, Sarah ; Fransen, Erik ; Huyghe, Jeroen ; 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. ; Makmura, Linna ; Ohmen, Jeffrey D. ; Linthicum, Frederick H. ; Fayad, Jose N. ; Pearson, John V. ; Craig, David W. ; Stephan, Dietrich A. ; Van Camp, Guy. / GRM7 variants confer susceptibility to age-related hearing impairment. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 4. pp. 785-796.
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AU - Van Eyken, Els

AU - Corneveaux, Jason J.

AU - Tembe, Waibhav D.

AU - Halperin, Rebecca F.

AU - Thorburn, Ashley Q.

AU - Thys, Sofie

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AU - Fransen, Erik

AU - Huyghe, Jeroen

AU - Pyykkö, Ilmari

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AU - Kremer, Hannie

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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 - Makmura, Linna

AU - Ohmen, Jeffrey D.

AU - Linthicum, Frederick H.

AU - Fayad, Jose N.

AU - Pearson, John V.

AU - Craig, David W.

AU - Stephan, Dietrich A.

AU - Van Camp, Guy

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