title: Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways.
abstract: 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.
  
  
  CONCLUSIONS
  These results provide new insights into the molecular basis of hearing function and may suggest new targets for hearing impairment treatment and prevention.
authors.affiliation: Medical Genetics, Department of Reproductive Sciences and Development, IRCCS-Burlo Garofolo, University of Trieste, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Girotto
authors.forename: Nicola
authors.initials: N
authors.lastname: Pirastu
authors.forename: Rossella
authors.initials: R
authors.lastname: Sorice
authors.forename: Ginevra
authors.initials: G
authors.lastname: Biino
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Adamo P
authors.initials: AP
authors.lastname: d'Adamo
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Hastie
authors.forename: Teresa
authors.initials: T
authors.lastname: Nutile
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Laura
authors.initials: L
authors.lastname: Portas
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Sheila
authors.initials: S
authors.lastname: Ulivi
authors.forename: Tatijana
authors.initials: T
authors.lastname: Zemunik
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Marina
authors.initials: M
authors.lastname: Ciullo
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Mario
authors.initials: M
authors.lastname: Pirastu
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001309:Auditory Threshold; D002352:Carrier Proteins / Q000235:genetics; D030541:Databases, Genetic; D000089742:Doublecortin-Like Kinases; D005060:Europe / Q000453:epidemiology; D005260:Female; D018703:Founder Effect; D008040:Genetic Linkage; D055106:Genome-Wide Association Study / Q000379:methods*; D006309:Hearing / Q000235:genetics*; D034381:Hearing Loss / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C540426:CMIP protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases; C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2