全基因组关联分析表明年龄相关性听力损失具有高度多基因性特征。
Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment.
作者信息
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, Friedman Rick A
机构信息
1] Center for Medical Genetics, University of Antwerp, Antwerp, Belgium [2] StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium.
Center for Medical Genetics, University of Antwerp, Antwerp, Belgium.
出版信息
Eur J Hum Genet. 2015 Jan;23(1):110-5. doi: 10.1038/ejhg.2014.56. Epub 2014 Jun 18.
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.
我们进行了一项全基因组关联研究（GWAS），以确定与年龄相关性听力损失（ARHI）相关的基因，ARHI是老年人中最常见的听力损失形式。对常见变异进行分析，包括对分层和环境协变量进行调整与未调整的情况、罕见变异及相互作用，以及基因集富集分析，均未发现具有全基因组显著性的变异。未发现任何先前报道基因的复制证据。一项关于遗传结构的研究首次表明，ARHI本质上是高度多基因的，可能不存在主要基因参与。该表型取决于大量单核苷酸多态性（SNP）的聚集效应，在适度规模的GWAS中，单个SNP的效应无法检测到。我们估计，数据集中22%的方差可由所有基因分型SNP的共同效应解释。一项评分分析显示，在P值低于0.01的SNP中，致病SNP有适度富集。
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