Hearing is complex trait but, until now, few genes are known to contribute to its variability and little is known about genetic factors involved in age-related hearing loss (ARHL). To discover genes and pathways underlying auditory function and ARHL we have planned an integrated strategy characterized by the following approaches: a) a GWAS meta-analyzing data from 6 isolated populations of quantitative traits. Results led to the identification of eight suggestive significant loci (p<10-7) with a series of genes expressed within the inner ear. Additional biological candidates (p<10-6) were identified. Some of these new loci map to already known hereditary hearing loss loci whose genes still need to be identified. Data have also been used to construct a highly significant "in silico" pathway for hearing function characterized by a network of 49 genes, 34 of which are certainly expressed in the ear; b) a similar GWAS on the same populations on qualitative traits leading to the identification of some loci on the following chromosomes 2,13,19,17,16,20 involving in some cases genes related with hearing development and hearing function but also genes whose function is still unknown. A replica phase is now in progress on a series of case/controls coming from different European countries; c) whole exome sequencing of cases selected from large pedigrees showing segregation of ARHL and coming from the same isolated populations. Preliminary results provide new insights into the molecular basis of hearing function and ARHL and may suggest new targets for hearing impairment treatment and prevention.
A genome-wide association study in European isolated populations identifies new loci and pathways for hearing function, thresholds and age-related loss
Rossella Sorice;Ginevra Biino;Teresa Nutile;Marina Ciullo;Mario Pirastu;
2011
Abstract
Hearing is complex trait but, until now, few genes are known to contribute to its variability and little is known about genetic factors involved in age-related hearing loss (ARHL). To discover genes and pathways underlying auditory function and ARHL we have planned an integrated strategy characterized by the following approaches: a) a GWAS meta-analyzing data from 6 isolated populations of quantitative traits. Results led to the identification of eight suggestive significant loci (p<10-7) with a series of genes expressed within the inner ear. Additional biological candidates (p<10-6) were identified. Some of these new loci map to already known hereditary hearing loss loci whose genes still need to be identified. Data have also been used to construct a highly significant "in silico" pathway for hearing function characterized by a network of 49 genes, 34 of which are certainly expressed in the ear; b) a similar GWAS on the same populations on qualitative traits leading to the identification of some loci on the following chromosomes 2,13,19,17,16,20 involving in some cases genes related with hearing development and hearing function but also genes whose function is still unknown. A replica phase is now in progress on a series of case/controls coming from different European countries; c) whole exome sequencing of cases selected from large pedigrees showing segregation of ARHL and coming from the same isolated populations. Preliminary results provide new insights into the molecular basis of hearing function and ARHL and may suggest new targets for hearing impairment treatment and prevention.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
