Title
Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairmentGenome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Translational Neurosciences (TNW)
Human molecular genetics
Publication type
article
Publication
Leiden,
Subject
Chemistry
Biology
Human medicine
Source (journal)
European journal of human genetics / European Society of Human Genetics. - Leiden
Volume/pages
23(2015):1, p. 110-115
ISSN
1018-4813
ISI
000346271500018
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/739c82/9ac9320.pdf
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