Abstract 16147: Racial and Ethnic Differences in the Diagnostic Yield of Cardiomyopathy, Aortopathy, and Arrhythmia Genetic Testing and Frequency of Family Variant Screening

Abstract

Introduction: Genetic testing for individuals with inherited cardiovascular conditions can guide treatment and aid in family screening. However, the diagnostic yield of pathogenic or likely pathogenic (P/LP) variants may differ by race and ethnicity because of a lack of diversity in population-based genomic databases. Methods: We evaluated the diagnostic yield (% tests with P/LP variants) of genetic testing for cardiomyopathy, aortopathy, and arrhythmia among probands undergoing testing at a large commercial laboratory (Invitae Corp.) from 9/2015-7/2022 for the most common racial and ethnic groups: Hispanic, Non-Hispanic (NH) Black, and NH White individuals. We used multivariable logistic regression to evaluate for differences in diagnostic yield by race and ethnicity adjusting for age, sex, payer, and number of genes tested. The ratio of the number of persons undergoing family variant testing (FVT) to the number with positive tests was determined, with Chi-square tests to evaluate for differences by group. Results: We identified 129,565 persons undergoing diagnostic genetic testing (n=9,157 Hispanic, n=16,287 NH Black, and n=78,740 NH White). Compared with White persons, the odds of a positive test were higher in Black and Hispanic persons for cardiomyopathy (OR 1.2, 95% CI 1.2-1.3, p <0.001 and OR 1.3, 95% CI 1.2-1.4, p <0.001, respectively) and aortopathy (OR 2.1, 95% CI 1.8-2.5, p <0.001 and OR 1.9, 95% CI 1.7-2.2, p <0.001, respectively), and higher for Hispanic persons for arrhythmia (OR 1.2, 95% CI 1.1-1.3, p <0.001). The ratio of FVT to positive tests was significantly (p < 0.001) lower for Black and Hispanic persons than White persons for cardiomyopathy (0.32, 1.19, and 1.51, respectively), aortopathy (0.77, 1.62, and 2.34, respectively), and arrhythmia (1.47, 2.23, and 3.33, respectively). Conclusion: Despite being underrepresented in population genomic databases, the diagnostic yield of genetic screening for cardiomyopathy and aortopathy was higher in Black and Hispanic persons compared with White individuals. The relative frequency of family variant testing was lower in Black and Hispanic than in White persons, indicating an opportunity to improve cascade screening in these groups.