title: A novel Z-score-based method to analyze candidate genes for age-related hearing impairment.
abstract: OBJECTIVE
  Approximately half of the variance of Age-Related Hearing Impairment (ARHI) is attributable to environmental risk factors, and the other half to genetic factors. None of these genes has ever been identified, but the genes involved in monogenic nonsyndromic hearing impairment are good candidates. Here we define and validate a quantitative trait value for ARHI, correcting for age and gender, to allow the genetic study of ARHI as a quantitative trait.
  
  
  METHODS
  Based on the ISO 7029 standard, we convert audiometric data into a Z-score, an age- and gender-independent value expressing to what extent a person is affected by ARHI. The validity of this approach is checked using a test population of randomly collected subjects. The power to evaluate the contribution of a candidate gene to ARHI is assessed using simulated populations. As an example, one ARHI candidate gene is analyzed.
  
  
  RESULTS
  In our test population, Z-scores were normally distributed although the mean did not equal zero. Z-scores were independent of age, and there was no difference between men and women. Power studies using simulated populations indicated that to detect moderate genetic effects, sample sizes of at least 500 random subjects are necessary.
  
  
  CONCLUSIONS
  The Z-score conversion appears to be a valid method to describe to what extent a subject is affected by ARHI, allowing to compare persons from different age and gender. This method can be the basis of future, powerful studies to identify ARHI genes.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.forename: Lut
authors.initials: L
authors.lastname: Van Laer
authors.forename: Nele
authors.initials: N
authors.lastname: Lemkens
authors.forename: Goele
authors.initials: G
authors.lastname: Caethoven
authors.forename: Kris
authors.initials: K
authors.lastname: Flothmann
authors.forename: Paul
authors.initials: P
authors.lastname: Govaerts
authors.forename: Paul
authors.initials: P
authors.lastname: Van de Heyning
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000704:Analysis of Variance; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold / Q000502:physiology*; D004777:Environment; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009622:Noise / Q000009:adverse effects; D011110:Polymorphism, Genetic; D011304:Presbycusis / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D012737:Sex Factors; D013223:Statistics as Topic / Q000379:methods
chemical_list: C110668:COCH protein, human; D016326:Extracellular Matrix Proteins; D011506:Proteins