title: Genetic variants in the peripheral auditory system significantly affect adult cochlear implant performance.
abstract: Cochlear implantation is an effective habilitation modality for adults with significant hearing loss. However, post-implant performance is variable. A portion of this variance in outcome can be attributed to clinical factors. Recent physiological studies suggest that the health of the spiral ganglion also impacts post-operative cochlear implant outcomes. The goal of this study was to determine whether genetic factors affecting spiral ganglion neurons may be associated with cochlear implant performance.
  
  
  
  Adults with post-lingual deafness who underwent cochlear implantation at the University of Iowa were studied. Pre-implantation evaluation included comprehensive genetic testing for genetic diagnosis. A novel score of genetic variants affecting genes with functional effects in the spiral ganglion was calculated. A Z-scored average of up to three post-operative speech perception tests (CNC, HINT, and AzBio) was used to assess outcome.
  
  
  
  Genetically determined spiral ganglion health affects cochlear implant outcomes, and when considered in conjunction with clinically determined etiology of deafness, accounts for 18.3% of the variance in postoperative speech recognition outcomes. Cochlear implant recipients with deleterious genetic variants that affect the cochlear sensory organ perform significantly better on tests of speech perception than recipients with deleterious genetic variants that affect the spiral ganglion.
  
  
  
  Etiological diagnosis of deafness including genetic testing is the single largest predictor of postoperative speech outcomes in adult cochlear implant recipients. A detailed understanding of the genetic underpinning of hearing loss will better inform pre-implant counseling. The method presented here should serve as a guide for further research into the molecular physiology of the peripheral auditory system and cochlear implants.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: A Eliot
authors.initials: AE
authors.lastname: Shearer
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Eppsteiner
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Frees
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Viral
authors.initials: V
authors.lastname: Tejani
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Sloan-Heggen
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Communication Sciences & Disorders, University of Iowa, Iowa City, IA, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Brown
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Communication Sciences & Disorders, University of Iowa, Iowa City, IA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Abbas
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Camille
authors.initials: C
authors.lastname: Dunn
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Marlan R
authors.initials: MR
authors.lastname: Hansen
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Gantz
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, IA, USA; Department of Molecular Physiology & Biophysics, University of Iowa College of Medicine, Iowa City, IA, USA. Electronic address: richard-smith@uiowa.edu.
authors.forename: Richard J H
authors.initials: RJH
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001299:Audiometry; D003051:Cochlea / Q000601:surgery; D019929:Cochlear Implantation; D003054:Cochlear Implants; D003638:Deafness / Q000235:genetics / Q000601:surgery*; D005260:Female; D014644:Genetic Variation; D023281:Genomics; D006309:Hearing / Q000502:physiology*; D034381:Hearing Loss / Q000601:surgery; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D008959:Models, Neurological; D009363:Neoplasm Proteins / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D013067:Speech Perception / Q000502:physiology; D013136:Spiral Ganglion / Q000502:physiology / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012697:Serine Endopeptidases; C409042:TMPRSS3 protein, human
keywords: Cochlear implant; Deafness; Genetics; Genomics