Racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing for sensorineural hearing loss

• Published in: Human genetics Vol. 141; no. 3-4; pp. 495 - 504
• Main Authors: Florentine, Michelle M., Rouse, Stephanie L., Stephans, Jihyun, Conrad, David, Czechowicz, Josephine, Matthews, Ian R., Meyer, Anna K., Nadaraja, Garani S., Parikh, Rajan, Virbalas, Jordan, Weinstein, Jacqueline E., Chan, Dylan K.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2022; Springer; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Child; Children; Cultural differences; Diagnosis; Ethnicity - genetics; Etiology; Gene Function; Genetic screening; Genetic Testing; Health aspects; Healthcare Disparities; Hearing loss; Hearing Loss, Sensorineural - diagnosis; Hearing Loss, Sensorineural - genetics; Hispanic or Latino - genetics; Hispanic people; Human Genetics; Humans; Medical colleges; Medical screening; Metabolic Diseases; Molecular Medicine; Original Investigation; Patients; Pediatrics; Retrospective Studies; The Molecular Genetics of Hearing and Deafness; United States; United States
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-021-02338-4

Understanding racial and ethnic disparities in diagnostic rates of genetic testing is critical for health equity. We sought to understand the extent and cause of racial and 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 genetic diagnoses were assigned for each patient, representing the likelihood of a genetic cause of hearing loss. Associations between 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 uncertain significance (VUS). Compared with White and Asian subjects, variants identified among Hispanic and Black children were less likely to be classified as pathogenic/likely pathogenic (15% vs. 24%, p  < 0.001), and Hispanic and Black children were less likely to have a definite genetic diagnosis (10% vs. 37%, p  < 0.001). The adjusted odds ratio for definite genetic diagnosis in Black and Hispanic children compared with White and Asian children was 0.19. Expanding genetic diagnostic criteria to include predicted deleterious VUSs reduced these disparities between White/Asian and Hispanic/Black children, with comparable molecular diagnostic rates (41% vs. 38%, p  = 0.72). However, in silico predictions are insufficiently valid for clinical use. Increased inclusion of underrepresented groups in genetic hearing-loss studies to clinically validate these variants is necessary to reduce racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing.