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 Pfister; Michael 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

doi:10.1093/hmg/ddn402

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

Institut for Klinisk Medicin

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

152 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Feb

Originalsprog	Engelsk
Tidsskrift	Human Molecular Genetics
Vol/bind	18
Udgave nummer	4
Sider (fra-til)	785-96
Antal sider	11
ISSN	0964-6906
DOI	https://doi.org/10.1093/hmg/ddn402
Status	Udgivet - 2009

Bibliografisk note

Keywords: Age Factors; Aged; Animals; Case-Control Studies; Ear, Inner; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Mice; Middle Aged; Polymorphism, Single Nucleotide; Presbycusis; Receptors, Kainic Acid

Adgang til dokumentet

10.1093/hmg/ddn402

Citationsformater

Friedman, R. A., Van Laer, L., Huentelman, M. J., Sheth, S. S., Van Eyken, E., Corneveaux, J. J., Tembe, W. D., Halperin, R. F., Thorburn, A. Q., Thys, S., Bonneux, S., Fransen, E., Huyghe, J., Pyykkö, I., Cremers, C. W. R. J., Kremer, H., Dhooge, I., Stephens, D., Orzan, E., ... Van Camp, G. (2009). GRM7 variants confer susceptibility to age-related hearing impairment. Human Molecular Genetics, 18(4), 785-96. 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.

I: Human Molecular Genetics, Bind 18, Nr. 4, 2009, s. 785-96.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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, bind 18, nr. 4, s. 785-96. 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. I: Human Molecular Genetics. 2009 ; Bind 18, Nr. 4. s. 785-96.

@article{9ccadd30791c11df928f000ea68e967b,

title = "GRM7 variants confer susceptibility to age-related hearing impairment",

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.",

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

note = "Keywords: Age Factors; Aged; Animals; Case-Control Studies; Ear, Inner; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Mice; Middle Aged; Polymorphism, Single Nucleotide; Presbycusis; Receptors, Kainic Acid",

year = "2009",

doi = "10.1093/hmg/ddn402",

language = "English",

volume = "18",

pages = "785--96",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - GRM7 variants confer susceptibility to age-related hearing impairment

AU - Friedman, Rick A

AU - Van Laer, Lut

AU - Huentelman, Matthew J

AU - Sheth, Sonal S

AU - Van Eyken, Els

AU - Corneveaux, Jason J

AU - Tembe, Waibhav D

AU - Halperin, Rebecca F

AU - Thorburn, Ashley Q

AU - Thys, Sofie

AU - Bonneux, Sarah

AU - Fransen, Erik

AU - Huyghe, Jeroen

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 - 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

N1 - Keywords: Age Factors; Aged; Animals; Case-Control Studies; Ear, Inner; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Mice; Middle Aged; Polymorphism, Single Nucleotide; Presbycusis; Receptors, Kainic Acid

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddn402

DO - 10.1093/hmg/ddn402

M3 - Journal article

C2 - 19047183

VL - 18

SP - 785

EP - 796

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 4

ER -