Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment
Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment
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.
Age Factors, Aged, Aged, 80 and over, Computational Biology, Databases, Genetic, Environment, Epistasis, Genetic, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Hearing Loss, Humans, Male, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Risk Factors, Signal Transduction, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
110-5
Fransen, Erik
b37f2016-1c9f-4b31-92e9-d18fc2e6f828
Bonneux, Sarah
c4ae11f3-6273-409c-b9da-0f2f19241f9f
Corneveaux, Jason J.
25f5eb8f-15a7-4837-8abd-d24772f6fa0d
Schrauwen, Isabelle
3364d6e4-f7a7-435c-8cff-6fc417a7f3a2
Di Berardino, Federica
be7e7821-065a-4563-a47c-faf13ff6314b
White, Cory H.
45233a78-f0c9-4696-8aaf-1b2673f83c91
Ohmen, Jeffrey D.
072b2de5-d335-4ba5-bc40-51744fbc1f92
Van de Heyning, Paul
1ea225ed-0c7e-4d2e-83c2-cdd3c4f42e69
Ambrosetti, Umberto
fca43bad-5c86-4809-935d-abd584174b0f
Huentelman, Matthew J.
f533a89e-4349-4653-bf79-07fe7454ed67
Van Camp, Guy
14d0a85c-0a0f-42d3-8324-02a4e6057d5d
Friedman, Rick A.
1500f8c3-af23-4558-bf96-b045fc280997
January 2015
Fransen, Erik
b37f2016-1c9f-4b31-92e9-d18fc2e6f828
Bonneux, Sarah
c4ae11f3-6273-409c-b9da-0f2f19241f9f
Corneveaux, Jason J.
25f5eb8f-15a7-4837-8abd-d24772f6fa0d
Schrauwen, Isabelle
3364d6e4-f7a7-435c-8cff-6fc417a7f3a2
Di Berardino, Federica
be7e7821-065a-4563-a47c-faf13ff6314b
White, Cory H.
45233a78-f0c9-4696-8aaf-1b2673f83c91
Ohmen, Jeffrey D.
072b2de5-d335-4ba5-bc40-51744fbc1f92
Van de Heyning, Paul
1ea225ed-0c7e-4d2e-83c2-cdd3c4f42e69
Ambrosetti, Umberto
fca43bad-5c86-4809-935d-abd584174b0f
Huentelman, Matthew J.
f533a89e-4349-4653-bf79-07fe7454ed67
Van Camp, Guy
14d0a85c-0a0f-42d3-8324-02a4e6057d5d
Friedman, Rick A.
1500f8c3-af23-4558-bf96-b045fc280997
Fransen, Erik, Bonneux, Sarah, Corneveaux, Jason J., Schrauwen, Isabelle, Di Berardino, Federica, White, Cory H., Ohmen, Jeffrey D., Van de Heyning, Paul, Ambrosetti, Umberto, Huentelman, Matthew J., Van Camp, Guy and Friedman, Rick A.
(2015)
Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment.
European Journal of Human Genetics, 23 (1), .
(doi:10.1038/ejhg.2014.56).
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.
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More information
Accepted/In Press date: 5 March 2014
e-pub ahead of print date: 18 June 2014
Published date: January 2015
Keywords:
Age Factors, Aged, Aged, 80 and over, Computational Biology, Databases, Genetic, Environment, Epistasis, Genetic, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Hearing Loss, Humans, Male, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Risk Factors, Signal Transduction, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
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Local EPrints ID: 413285
URI: http://eprints.soton.ac.uk/id/eprint/413285
ISSN: 1018-4813
PURE UUID: 7f31e84c-5863-4f61-9734-7451d9ecc1b9
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Date deposited: 18 Aug 2017 16:32
Last modified: 15 Mar 2024 12:42
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Contributors
Author:
Erik Fransen
Author:
Sarah Bonneux
Author:
Jason J. Corneveaux
Author:
Isabelle Schrauwen
Author:
Federica Di Berardino
Author:
Cory H. White
Author:
Jeffrey D. Ohmen
Author:
Paul Van de Heyning
Author:
Umberto Ambrosetti
Author:
Matthew J. Huentelman
Author:
Guy Van Camp
Author:
Rick A. Friedman
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