Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways

Giorgia Girotto (1) , Nicola Pirastu (1) , Rossella Sorice (2) , Ginevra Biino (3) , Harry Campbell (4) , Adamo P. d'Adamo (1) , Nicholas D. Hastie (5) , Teresa Nutile (2) , Ozren Polasek (4) , Laura Portas (6) , Igor Rudan (4) , Sheila Ulivi (1) , Tatijana Zemunik (7) , Alan F. Wright (8) , Marina Ciullo (2) , Caroline Hayward (9) , Mario Pirastu (3) , Paolo Gasparini (1)

1 Università degli studi di Trieste = University of Trieste
2 Institute of Genetics and Biophysics, CNR, Naples
3 Institute of Pop. Genetics, CNR, Sassari;Shardna life science Pula Cagliari
4 Edin. - University of Edinburgh
5 MRC Human Gentics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital
6 Institute of Pop. Genetics, CNR, Sassari
7 Croatian Global Health Research Center; University of Split Medical School
8 MRC Human Gentics Unit, Inst Genet and Mol Med, Western General Hospital, Edinburgh
9 MRC Human Gentics Unit, Inst Genet and Mol Med, Western General Hospital, Edinburgh

Hearing is complex trait, but until now only 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 by meta-analyzing data from 6 isolated populations of European ancestry for an overall number of 3417 individuals. 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 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 characterized by a network of 49 genes, 34 of which are certainly expressed in the ear. These results provide new insights into the molecular basis of hearing function and may suggest new targets for hearing impairment treatment and prevention

Mots clés: Molecular genetics; Genetic epidemiology

Giorgia Girotto, Nicola Pirastu, Rossella Sorice, Ginevra Biino, Harry Campbell, et al.. Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways. Journal of Medical Genetics, 2011, 48 (6), pp.369. ⟨10.1136/jmg.2010.088310⟩. ⟨hal-00623287⟩