Transcript PPT

Clinical Challenges in Identifying
Noise-Induced Hearing Loss
(NIHL) Phenotype for
Genetic Association
Analysis
Presenter
Ishan Bhatt, Ph.D., CCC-A
Coauthors/Contributors
O’neil Guthrie, Ph.D., CCC-A
Michael Skelton, Ph.D., CCC-A, FAAA
Viacheslav Fofanov, Ph.D.
Srinivas Kosaraju, Ph.D.
Omar Badreddin, Ph.D.
Disclosure
We have no relevant financial or nonfinancial relationships to
disclose
Complex Disorders
Complex disorders: multiple
factorial disorders
Their causes: multiple genes in
combination with lifestyle and
environmental factors
No clear-cut pattern of
inheritance
Family Clustering
NIHL is a Complex Disease
Gene
Challenging to estimate a
person's risk of inheriting
or passing on NIHL
causing genes
Environment
Some individuals are
more susceptible to noise
than others
Gene-environment
interaction
Importance of Phenotyping NIHL
Success of gene mapping lies
on the ability to define the
target phenotype (i.e. trait
of a disease) with accuracy
and precision
A well-defined phenotype
can improve sensitivity and
specificity of geneenvironment association
studies
Early Efforts: Phenotyping NIHL
Definition: Absolute
audiometric thresholds at
high frequencies (3 to 8
kHz)
Industrial population
Confounding variables
(Sliwinska-Kowalska & Pawelczyk, 2013; Konings et al., 2006)
Recent Efforts: Phenotyping NIHL
Notch: A drop in hearing sensitivity at 4 to 6 kHz
of at least 15 dB from the self-referenced
previous best threshold in a linear progression of
frequencies, with a recovery of at least 5 dB after
the notch
NIHL phenotype = Bilateral notches
College-aged student musicians for better control
over confounding variables
Audiometric Notch
Phillips et al. (2015)
Is NIHL Overestimated?
Almost 45% of college-aged musicians showed an
audiometric notch at least in one ear. Almost 12%
showed bilateral notches (Phillip et al., 2010)
Most notches occurred at 6000 Hz
A previous study argued that “sensitive” notch
definition especially including unweighted 6000 Hz
threshold (used by Niskar et al, 2001) may lead to
high false positives (Schlauch & Carney, 2011)
Aims of the Study
To study the prevalence and associated factors of
the audiometric notch in US youth (12-19 years)
To examine the possibility of overestimating the
audiometric notch defined as the NIHL phenotype
in our previous study (Phillips et al, 2015)
Methods
Demographic and audiometric databases from
NHANCES (2005-10)
Participants aged 12-19 years; Bilateral otoscopy:
No abnormality detected
Tympanogram: compliance value from 0.2 to 1.8 cc,
and MEP value from -50 to 25 dapa in both ears
were considered for the study
Total participants for the analysis: 2348
Computer-Simulated Audiograms
Step 1:
Truncated Normal Distribution
Step 2:
“Actual” Audiogram Simulation
Mean= 0
SD = 7.5
Simulate 3000 values
Selected value was used
as person’s “actual threshold”
Selected “actual threshold” value
for this example is 0 dB HL
-10 dB HL
5 dB added in the selected value
to derive “actual threshold” at
6000 and 8000 Hz
(Schlauch & Carney, 2011)
Computer-Simulated Audiograms
Step 3: Sensory Threshold
Simulation
“sensory thresholds” were
simulated by selecting a random
value from the normal curve
Step 4: Rounding
 Sensory thresholds
were rounded to
nearest 5 dB value
 Threshold lower than
-10 dB HL were
rounded to -10 dB HL
Mean= Actual Threshold
SD = 5
(Schlauch & Carney, 2011)
Aim 1: Result
Prevalence of bilateral
notch was 16.6%
in a general population
aged 12-19 years
Aim 2: Result
Estimated
false positive rate:
At least 5.5%
Audiometric Notch
(NHANES:2005-10)
Almost 93% simulated notched audiograms
showed 15-20 dB of notch depth
Audiometric Notch: Associated
Factors
Associated Variables
Unilateral Notch
(Odds Ratio)
Associated Variables
Bilateral Notch
(Odds Ratio)
Males < Females
0.753
(0.618-0.918)
Males < Females
0.585
(0.450-0.761)
African Americans <
European Americans
0.700
(0.538-0.911)
African Americans <
European Americans
0.537
(0.376-0.767)
14-15 years > 18-19
years
0.753
(0.618-0.918)
Noisy Job > No noisy job
1.836
(1.097-3.074)
Music exposure, firearm exposure, smoking, family income and
tinnitus showed no association with the audiometric notch
Discussion
Almost 42% of the participants showed an
audiometric notch without reporting a history of a
noisy job, music exposure, firearm noise exposure
and acoustic exposure before audiometry.
Participants aged 12-13 years showed 40%
prevalence of unilateral notch and 13.5%
prevalence of bilateral notch
Prevalence of audiometric notch in US youth (12-19
years) was higher than its prevalence in collegeaged musicians
Discussion(continue)
Phillips et al (2010 & 2015) and NHANES used TDH
50 type supra-aural transducers
 Supra-aural transducers show poor test-retest
reliability at high frequencies especially around
6000 Hz (Mello et al, 2015)
Standing waves in the ear canal is a candidate
mechanism for high false positive rates observed in
the NHANES data
References
Gerhardt, K. J., Rodriguez, G. P., Hepler, E. L. & Moul. 1987. Ear canal volume and variability in the patterns of temporary threshold
shifts. Ear and hearing. 8(6), 316-321.
Konings, A., Van Laer, L. & Van Camp, G. 2009. Genetic studies on noise-induced hearing loss: a review. Ear and hearing, 30(2),
151-159.
Mello, L., da Silva, Gil, D. 2015. Test-retest variability in the pure tone audiometry: comparison between two transducers. Audiol
Commun Res, 20(3), 239-245.
Niskar, A.S., Kieszak, S.M., Holmes, A.E., Esteban, E., Rubin, C. & Brody, D.J. 2001. Estimated prevalence of noise-induced hearing
threshold shifts among children 6 to 19 years of age: the Third National Health and Nutrition Examination Survey,
1988-1994, United States. Pediatrics, 108(1), 40-43.
Phillips S.L., Henrich V.C. & Mace S.T. 2010. Prevalence of noise-induced hearing loss in student musicians. Int J Audiol, 49, 309–31
Phillips, S.L., Richter, S.J., Teglas, S.L., Bhatt, I.S. et al. (2015). Feasibility of a bilateral 4000-6000 Hz notch as a phenotype for
genetic association analysis. IJA, 54(10), 645-652.
Schlauch, R. & Carney, E. (2011). Are False-Positive Rates Leading to an Overestimation of Noise-Induced Hearing Loss? JSLHR, 54,
679-692.
Sliwinska-Kowalska, M. & Pawelczyk, M. 2013. Contribution of genetic factors to noise-induced hearing loss: a human studies
review. Mutation research, 752(1), 61-65.