A novel Z-score-based method to analyze candidate genes for age-related hearing impairment.
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.
Fransen
Erik
E
Department of Medical Genetics, University of Antwerp, Belgium.
Van Laer
Lut
L
Lemkens
Nele
N
Caethoven
Goele
G
Flothmann
Kris
K
Govaerts
Paul
P
Van de Heyning
Paul
P
Van Camp
Guy
G
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
C110668:COCH protein, human; D016326:Extracellular Matrix Proteins; D011506:Proteins