Dataset Information

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.

SUBMITTER: Friedman RA

PROVIDER: S-EPMC2638831 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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GRM7 variants confer susceptibility to age-related hearing impairment.

Friedman Rick A RA Van Laer Lut L Huentelman Matthew J MJ Sheth Sonal S SS Van Eyken Els E Corneveaux Jason J JJ Tembe Waibhav D WD Halperin Rebecca F RF Thorburn Ashley Q AQ Thys Sofie S Bonneux Sarah S Fransen Erik E Huyghe Jeroen J Pyykkö Ilmari I Cremers Cor W R J CW Kremer Hannie H Dhooge Ingeborg I Stephens Dafydd D Orzan Eva E Pfister Markus M Bille Michael M Parving Agnete A Sorri Martti M Van de Heyning Paul H PH Makmura Linna L Ohmen Jeffrey D JD Linthicum Frederick H FH Fayad Jose N JN Pearson John V JV Craig David W DW Stephan Dietrich A DA Van Camp Guy G

Human molecular genetics 20081201 4

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 5 ...[more]

PMID: 19047183

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Project description:Age-related hearing loss has been associated with increased recruitment of frontal brain areas during speech perception to compensate for the decline in auditory input. This additional recruitment may bind resources otherwise needed for understanding speech. However, it is unknown how increased demands on listening interact with increasing cognitive demands when processing speech in age-related hearing loss. The current study used a full-sentence working memory task manipulating demands on working memory and listening and studied untreated mild to moderate hard of hearing (n = 20) and normal-hearing age-matched participants (n = 19) with functional MRI. On the behavioral level, we found a significant interaction of memory load and listening condition; this was, however, similar for both groups. Under low, but not high memory load, listening condition significantly influenced task performance. Similarly, under easy but not difficult listening conditions, memory load had a significant effect on task performance. On the neural level, as measured by the BOLD response, we found increased responses under high compared to low memory load conditions in the left supramarginal gyrus, left middle frontal gyrus, and left supplementary motor cortex regardless of hearing ability. Furthermore, we found increased responses in the bilateral superior temporal gyri under easy compared to difficult listening conditions. We found no group differences nor interactions of group with memory load or listening condition. This suggests that memory load and listening condition interacted on a behavioral level, however, only the increased memory load was reflected in increased BOLD responses in frontal and parietal brain regions. Hence, when evaluating listening abilities in elderly participants, memory load should be considered as it might interfere with the assessed performance. We could not find any further evidence that BOLD responses for the different memory and listening conditions are affected by mild to moderate age-related hearing loss.

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GRM7 variants confer susceptibility to age-related hearing impairment.

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GRM7 variants confer susceptibility to age-related hearing impairment.

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