Racial Disparities in Genetic Detection Rates for Inherited Retinal Diseases

Academic Background

Inherited retinal diseases (IRDs) are a group of degenerative retinal disorders caused by genetic mutations, which can lead to vision loss or even blindness. With advances in gene discovery and next-generation DNA sequencing, an increasing number of patients can obtain definitive genetic diagnoses through genetic testing. These diagnoses not only help confirm the disease and predict prognosis but also provide critical information for genetic counseling, reproductive decision-making, and eligibility for clinical trials. However, it remains unclear whether the detection rates of current genetic testing platforms are consistent across different racial groups. In the field of cancer genetics, studies have shown that African ancestry is associated with a higher proportion of inconclusive results in BRCA1/BRCA2 breast cancer genetic testing. However, in IRD research, few studies have disclosed the racial composition of participants, and even fewer have compared genetic detection rates among patients of different racial backgrounds.

Therefore, this study aims to investigate the differences in genetic detection rates between Black and non-Hispanic White patients with IRDs and to analyze the impact of race, age, sex, phenotype, and gene panel size on detection rates. This research is significant for understanding the effectiveness of genetic testing across different racial groups, especially as future treatments continue to develop, ensuring that all patients have equitable access to genetic diagnosis and treatment opportunities.

Source of the Paper

This paper was co-authored by Rebhi O. Abuzaitoun, Kari H. Branham, Gabrielle D. Lacy, and others, from institutions such as the University of Michigan and Blueprint Genetics. The paper was published online on November 7, 2024, in JAMA Ophthalmology, with the DOI 10.1001/jamaophthalmol.2024.4696.

Study Design and Methods

Study Design

This study is a retrospective case series, with data collected from the University of Michigan (UM) and Blueprint Genetics (BG). Data collection at UM spanned from October 30, 2013, to October 26, 2022. The study included 572 patients, of whom 295 were male (51.6%), with a mean age of 45 years. Among the patients, 54 were Black (9.4%) and 518 were White (90.6%). The primary objective was to compare the genetic detection rates between Black and White patients with IRDs.

Data Collection and Processing

At UM, inclusion criteria were: 1) a clinical diagnosis of IRDs; 2) wide-panel genetic testing; and 3) both the patient and their parents self-identified as the same race (Black or non-Hispanic White). Data were obtained through electronic medical records, including patient age, sex, race, phenotype, genetic test results, and the number of genes tested. Genetic test results were categorized as positive (detection of pathogenic or likely pathogenic variants), negative (no variants detected), or inconclusive (detection of variants of uncertain significance).

In the BG database, the study included 320 Black patients and 2,931 White patients, comparing the genetic detection rates between the two groups. Statistical analysis methods included logistic regression and chi-square tests.

Main Results

University of Michigan Data Analysis

Among the 572 patients at UM, 389 (68%) had positive genetic test results. The positive detection rate was significantly lower in Black patients compared to White patients (38.9% vs. 71%, p < 0.001). Additionally, for every 10-year increase in age, the positive detection rate decreased by 16% (OR = 0.84, 95% CI: 0.76-0.92, p < 0.001). Phenotype analysis showed that patients with cone/cone-rod dystrophy had a significantly lower positive detection rate compared to those with rod-cone dystrophy (OR = 0.45, 95% CI: 0.27-0.73, p = 0.001).

Blueprint Genetics Data Analysis

Among the 3,251 patients in the BG database, 320 were Black (9.7%). The positive detection rate for Black patients was 44.4%, significantly lower than the 57.7% rate for White patients (χ2 = 18.65, p < 0.001).

Discussion and Conclusions

Impact of Racial Disparities

This study found that Black patients had significantly lower positive detection rates in IRD genetic testing compared to White patients. This result is consistent with previous studies, indicating that current genetic testing tools have lower detection rates in Black populations. This may be due to the lower frequency or insufficient study of certain genetic variants in Black populations. Additionally, older patients and those with cone/cone-rod dystrophy also had lower positive detection rates.

Limitations of the Study

This study has several limitations. First, the gene panel sizes and testing methods varied across different laboratories, which may affect the consistency of results. Second, the sample size of Black patients was relatively small, potentially limiting the statistical power of the analysis. Furthermore, the study did not include other racial groups, and future research should expand the sample size to validate these findings.

Significance of the Study

This study highlights the racial disparities in IRD genetic testing, particularly the lower detection rates in Black patients. As future treatments continue to develop, it is crucial to ensure that all patients have equitable access to genetic diagnosis and treatment opportunities. The findings suggest that future genetic testing platforms need to pay more attention to genetic variants in minority populations to improve the accuracy and fairness of testing.

Highlights of the Study

1. First Systematic Study on Racial Disparities: This study is the first to systematically compare genetic detection rates between Black and White patients with IRDs, filling a gap in this field of research.
2. Impact of Age and Phenotype: The study found that older patients and those with cone/cone-rod dystrophy had lower positive detection rates, providing important insights for future clinical diagnoses.
3. Need for Improvement in Genetic Testing Platforms: The results suggest that current genetic testing platforms have lower detection rates in minority populations, and future improvements in testing technology are needed to enhance fairness.

Conclusion

This study demonstrates that Black patients have significantly lower positive detection rates in IRD genetic testing compared to White patients, and older patients and those with cone/cone-rod dystrophy also have lower detection rates. These findings underscore the issue of racial disparities in genetic testing and highlight the need for future improvements in testing technology to ensure equitable access to genetic diagnosis and treatment opportunities for all patients.