TY - JOUR T1 - Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways. JF - J Med Genet Y1 - 2011 A1 - Girotto, Giorgia A1 - Pirastu, Nicola A1 - Sorice, Rossella A1 - Biino, Ginevra A1 - Campbell, Harry A1 - d'Adamo, Adamo P A1 - Hastie, Nicholas D A1 - Nutile, Teresa A1 - Polasek, Ozren A1 - Portas, Laura A1 - Rudan, Igor A1 - Ulivi, Sheila A1 - Zemunik, Tatijana A1 - Wright, Alan F A1 - Ciullo, Marina A1 - Hayward, Caroline A1 - Pirastu, Mario A1 - Gasparini, Paolo KW - Adaptor Proteins, Signal Transducing KW - Animals KW - Auditory Threshold KW - Carrier Proteins KW - Databases, Genetic KW - Europe KW - European Continental Ancestry Group KW - Female KW - Founder Effect KW - Genetic Linkage KW - Genome-Wide Association Study KW - Hearing KW - Hearing Loss KW - Humans KW - Intracellular Signaling Peptides and Proteins KW - Male KW - Mice KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Protein-Serine-Threonine Kinases KW - Receptor-Like Protein Tyrosine Phosphatases, Class 2 KW - Receptors, Metabotropic Glutamate AB -

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.

VL - 48 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21493956?dopt=Abstract ER -