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Eur J Hum Genet. 2015 Jan;23(1):110-5. doi: 10.1038/ejhg.2014.56. Epub 2014 Jun 18.

Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment.

Author information

1
1] Center for Medical Genetics, University of Antwerp, Antwerp, Belgium [2] StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium.
2
Center for Medical Genetics, University of Antwerp, Antwerp, Belgium.
3
Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
4
1] Center for Medical Genetics, University of Antwerp, Antwerp, Belgium [2] StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium [3] Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
5
1] Audiology Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy [2] Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
6
Cell Biology and Genetics Division, House Research Institute, Los Angeles, CA, USA.
7
Department of Otolaryngology, University Hospital of Antwerp, Edegem, Belgium.

Abstract

We performed a genome-wide association study (GWAS) to identify the genes responsible for age-related hearing impairment (ARHI), the most common form of hearing impairment in the elderly. Analysis of common variants, with and without adjustment for stratification and environmental covariates, rare variants and interactions, as well as gene-set enrichment analysis, showed no variants with genome-wide significance. No evidence for replication of any previously reported genes was found. A study of the genetic architecture indicates for the first time that ARHI is highly polygenic in nature, with probably no major genes involved. The phenotype depends on the aggregated effect of a large number of SNPs, of which the individual effects are undetectable in a modestly powered GWAS. We estimated that 22% of the variance in our data set can be explained by the collective effect of all genotyped SNPs. A score analysis showed a modest enrichment in causative SNPs among the SNPs with a P-value below 0.01.

PMID:
24939585
PMCID:
PMC4266741
DOI:
10.1038/ejhg.2014.56
[Indexed for MEDLINE]
Free PMC Article

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