IMPORTANCE It is important to determine what frequencies and auditory perceptual measures are the most sensitive early indicators of noise-induced hearing impairment.OBJECTIVES To examine whether hearing loss among shipyard workers increases more rapidly at extended high frequencies than at clinical frequencies and whether subtle auditory processing deficits are present in those with extensive noise exposure but little or no hearing loss. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional study collected audiometric data (0.25-16 kHz), survey questionnaires, and noise exposure levels from 7890 shipyard workers in a Shanghai shipyard from 2015 to 2019. Worsening hearing loss was evaluated in the group with hearing loss. Speech processing and temporal processing were evaluated in 610 participants with noise exposure and clinically normal hearing to identify early biomarkers of noise-induced hearing impairment. Data analysis was conducted from November to December 2020. MAIN OUTCOMES AND MEASURES Linear regression was performed to model the increase in hearing loss as function of cumulative noise exposure and compared with a group who were monitored longitudinally for 4 years. Auditory processing tests included speech-in-noise tests, competing sentence tests, dichotic listening tests, and gap detection threshold tests and were compared with a control group without history of noise exposure. RESULTS Of the 5539 participants (median [interquartile range (IQR)] age, 41.0 [34.0-47.0] years;3861 [86.6%] men) included in the cross-sectional analysis, 4459 (80.5%) were hearing loss positive and 1080 (19.5%) were hearing loss negative. In younger participants (ie, Յ40 years), the maximum rate of increase in hearing loss was 0.40 (95% CI, 0.39-0.42) dB per A-weighted dB-year (dB/dBAyear) at 12.5 kHz, higher than the growth rates of 0.36 (95% CI, 0.35-0.36) dB/dBA-year at 4 kHz, 0.32 (95% CI, 0.31-0.33) dB/dBA-year at 10 kHz, 0.31 (95% CI, 0.30-0.31) dB/dBA-year at 6 kHz, 0.27 (95% CI, 0.26-0.27) dB/dBA-year at 3 kHz, and 0.27 (95% CI, 0.27-0.28) dB/dBA-year at 8 kHz. In the 4-year longitudinal analysis of hearing loss among 403 participants, the mean (SD) annual deterioration in hearing was 2.70 (2.98) dB/y at 12.5 kHz, almost twice as that observed at lower frequencies (eg, at 3kHz: 1.18 [2.15] dB/y). The auditory processing scores of participants with clinically normal hearing and a history of noise exposure were significantly lower than those of control participants (eg, median [IQR] score on speech-in-noise test, noise-exposed group 1 vs
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Background: The overall genetic profile for noise-induced hearing loss (NIHL) remains to be explored. Here we used a novel machine learning (ML) strategy to evaluate individual susceptibility to NIHL and identify the underlying genetic variants based on a subsample of participants with extreme phenotype. Methods: Demographic and audiometric data of 5,539 shipbuilding workers from large cross-sectional surveys were included in four ML algorithms to predict the hearing level. The area under the curve (AUC) and prediction accuracy were used to assess the performance of the classification models. We screened 300 participants that were misclassified by all of the four ML models, with extreme phenotypes implying they were either highly susceptible or resistant to NIHL and used whole-exome sequencing (WES) to identify the underlying variants associated with NIHL risk among the NIHL-susceptible and NIHL-resistant individuals. Subsequently, candidate risk loci were validated in a large independent noise-exposed cohort, followed by a meta-analysis.Results: With 10-fold cross-validation, the performances of the four ML models were robust and similar, with average AUC and accuracy ranging from 0.783 to 0.798 and 73.7% to 73.8%, respectively. The phenotypes of the NIHL-susceptible group and NIHL-resistant group were significantly different (all p<0.001). After WES analysis and filtering, 12 novel variants contributing to NIHL susceptibility were identified and replicated. The meta-analyses shown that the rs41281334 A allele of CDH23 (OR=1.506, 95% CI=1.106-2.051) and the rs12339210 C allele of WHRN (OR=3.06, 95% CI=1.398-6.700) were significantly associated with increased risk of NIHL after adjustment for conventional risk factors.Conclusions: This study determined two novel genetic variants in CDH23 rs41281334 and WHRN rs12339210 associated with NIHL risk, based on a potential approach for evaluating individual susceptibility using ML models. Trial registration: Chinese Clinical Trial Registry (registration number: ChiCTR-RPC-17012580)
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