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

被引：67

作者：

Fransen, Erik ^{[1
,2
]}

Bonneux, Sarah ^{[1
]}

Corneveaux, Jason J. ^{[3
]}

Schrauwen, Isabelle ^{[1
,2
,3
]}

Di Berardino, Federica ^{[4
,5
]}

White, Cory H. ^{[6
]}

Ohmen, Jeffrey D. ^{[6
]}

Van de Heyning, Paul ^{[7
]}

Ambrosetti, Umberto ^{[4
,5
]}

Huentelman, Matthew J. ^{[3
]}

Van Camp, Guy ^{[1
]}

Friedman, Rick A. ^{[6
]}

机构：

[1] Univ Antwerp, Ctr Med Genet, B-2610 Antwerp, Belgium

[2] Univ Antwerp, StatUa Ctr Stat, B-2610 Antwerp, Belgium

[3] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA

[4] Univ Milan, Dept Clin Sci & Community Hlth, Audiol Unit, Milan, Italy

[5] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

[6] House Res Inst, Cell Biol & Genet Div, Los Angeles, CA USA

[7] Univ Antwerp Hosp, Dept Otolaryngol, Edegem, Belgium

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2015年 / 23卷 / 01期

关键词：

HUMAN HEIGHT; EXPRESSION; PATHWAYS; LOCI;

D O I：

10.1038/ejhg.2014.56

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：110 / 115

页数：6

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