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Original article
Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways
  1. Giorgia Girotto1,
  2. Nicola Pirastu1,
  3. Rossella Sorice2,
  4. Ginevra Biino3,4,
  5. Harry Campbell5,
  6. Adamo P d'Adamo1,
  7. Nicholas D Hastie6,
  8. Teresa Nutile2,
  9. Ozren Polasek5,7,
  10. Laura Portas3,
  11. Igor Rudan5,7,
  12. Sheila Ulivi1,
  13. Tatijana Zemunik7,
  14. Alan F Wright6,
  15. Marina Ciullo2,
  16. Caroline Hayward6,
  17. Mario Pirastu3,4,
  18. Paolo Gasparini1
  1. 1Medical Genetics, Department of Reproductive Sciences, Development and Public Health, IRCCS-Burlo Garofolo Children Hospital, Unversity of Trieste, Trieste, Italy
  2. 2Institute of Genetics and Biophysics “A.Buzzati-Traverso”, CNR, Naples, Italy
  3. 3Institute of Population Genetics, National Research Council of Italy, Sassari, Italy
  4. 4Shardna life science, Pula, Cagliari, Italy
  5. 5Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, UK
  6. 6MRC Human Gentics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK
  7. 7Croatian Centre for Global Health, University of Split Medical School, Split, Croatia
  1. Correspondence to Paolo Gasparini, Medical Genetics, Department of Reproductive Sciences and Development, IRCCS-Burlo Garofolo, University of Trieste, Via dell'Istria 65, Trieste 34100, Italy; gasparini{at}


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
  • GWAS
  • meta-analysis
  • isolated populations
  • ‘in silico’ pathways
  • molecular genetics
  • genetic epidemiology

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Supplementary materials


  • 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.