Background Hearing is a complex trait, but until now only a few genes are known to contribute to variability of this process. In order to discover genes and pathways that underlie auditory function, a genome-wide association study was carried out within the International Consortium G-EAR.
Methods Meta-analysis of genome-wide association study's data from six isolated populations of European ancestry for an overall number of 3417 individuals.
Results Eight suggestive significant loci (p<10−7) were detected with a series of genes expressed within the inner ear such as: DCLK1, PTPRD, GRM8, CMIP. Additional biological candidates marked by a single nucleotide polymorphism (SNP) with a suggestive association (p<10−6) were identified, as well as loci encompassing ‘gene desert regions’—genes of unknown function or genes whose function has not be linked to hearing so far. 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 characterised by a network of 49 genes, 34 of which are certainly expressed in the ear.
Conclusion These results provide new insights into the molecular basis of hearing function and may suggest new targets for hearing impairment treatment and prevention.
- Molecular basis of hearing system
- isolated populations
- ‘in silico’ pathways
- molecular genetics
- genetic epidemiology
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GG and NP contributed equally.
Funding The study was partially funded by Telethon Foundation (GGP09037), Fondo Trieste (2008), Regione FVG (L.26.2008), and Italian Ministry of Health (RC16/06) (to PG). The KORCULA-CROATIA study in the Croatian island of Vis was supported through the grants from the Medical Research Council UK to HC, AFW and IR; and Ministry of Science, Education and Sport of the Republic of Croatia to IR. (number 108-1080315-0302). The SPLIT-CROATIA study was supported through the grants from the Medical Research Council UK; and Ministry of Science, Education and Sport of the Republic of Croatia. (number 108-1080315-0302). The Cilento study was supported by grants from the Italian Ministry of Universities (FIRB -RBIN064YAT) and the Ente Parco Nazionale del Cilento e Vallo di Diano to MC. RS was supported by a fellowship of Regione Campania, Italy.
Competing interests None.
Patient consent Obtained
Ethics approval Each population study participating to the consortium has been approved by the local ethical committee.
Provenance and peer review Not commissioned; externally peer reviewed.