Racial and Ethnic Disparities in Diagnostic Efficacy of Comprehensive Genetic Testing for Sensorineural Hearing Loss

Abstract Understanding racial/ethnic disparities in diagnostic rates of genetic testing is critical for health equity. We sought to understand the extent and cause of racial/ethnic disparities in diagnostic efficacy of comprehensive genetic testing (CGT) for sensorineural hearing loss (SNHL). We performed a retrospective cohort study at two tertiary children’s hospitals on a diverse cohort of 240 consecutive pediatric patients (76% publicly insured, 82% non-White) with SNHL of unknown etiology who underwent CGT. Definite and possible molecular diagnoses were assigned for each patient, representing the likelihood of a genetic cause of hearing loss. Associations between race/ethnicity and diagnostic rates were examined. 3.8 ± 2.1 variants were detected per patient; this frequency did not vary between White/Asian and Hispanic/Black cohorts. Overall, 82% of variants were Variants of Unknown Significance (VUS). Compared with White/Asian subjects, variants identified among Hispanic/Black children were less likely to be known (15% vs. 24%, p < 0.001), and Hispanic/Black children were less likely to have a definite molecular diagnosis (10% vs. 37%, p < 0.001). Expanding molecular diagnostic criteria to include predicted deleterious VUSs reduced these disparities between White/Asian and Hispanic/Black children, with comparable molecular diagnostic rates (41% vs. 35%, p = 0.46). The adjusted odds ratio for definite genetic diagnosis in Black/Hispanic children compared with White/Asian children was 0.18. These results demonstrate the extent of racial/ethnic disparities in diagnostic efficacy of comprehensive genetic testing. Consideration of deleterious VUSs reduced these disparities, highlighting the need for increased inclusion of underrepresented groups in genetic hearing-loss studies to clinically validate these variants.