B-203 Advancing Equity, Inclusion, and Diversity in Genetic Testing: Disparities in Detection Rates and Access to Carrier Screening Among 8,000 Patients Nationwide
Authors: Hasadsri L , Winters J L , McDonald A M , Harrington S C , Kuennen R , Thieke S , Stelmach E , Cabral H , Hayman J , Meyer M , Rumilla K 
Published: October 2024

Background

Professional medical societies recommend that carrier screening for 113 different genetic disorders be offered during pregnancy or preconception to all individuals, regardless of ancestry, in order to provide more equitable opportunities for patients to ascertain their reproductive risks. In our clinical laboratory experience, however, the vast majority of healthcare providers continue to order carrier screening for only cystic fibrosis (CF), which is disproportionately common in white individuals of Northern European descent. Our highest volume CF screening test is performed on &gt;10,500 diverse patients per year and utilizes a targeted genotyping array that detects &gt;500 variants in CFTR and &gt;1200 variants in &gt;150 other pertinent genes. Here we report the inequities in diagnostic yield among our first 8,000 patients for whom only limited testing was ordered and examine the barriers to widespread adoption of more inclusive carrier screening.

Methods

Three carrier screening options (CF, CF+spinal muscular atrophy [SMA], CF+SMA+fragile X syndrome [FXS]+hemoglobinopathies) were ordered clinically and performed on DNA extracted from 8,000 whole blood samples from unique individuals utilizing a custom SNP array (Thermo Fisher GeneTitanTM platform) designed to detect &gt;1700 pathogenic variants in 218 different genes. Data was retrospectively reviewed to determine overall detection rates for carriers of all recommended conditions vs. only the condition(s) included in the originally ordered service. Finally, reproductive health providers at nine different ordering sites across the U.S. were interviewed regarding their current carrier screening practices.

Results

Patients were referred for testing by 119 different clinical facilities. 98.1% (7847/8000) had CF-only testing ordered, 1.2% (99/8000) had CF+SMA testing ordered, and 0.68% (54/8000) had testing for CF+SMA+FXS+hemoglobinopathies ordered. 7.1% (568/8000) of patients had reportable variants in CFTR. Had CF+SMA testing been ordered on all 8,000 patients, however, the diagnostic yield would have been 8.9%. Of the patients who had CF-only or CF+SMA testing ordered, 11.9% (943/7946) were found to be carriers of hemoglobinopathies. Finally, had all 8000 patients had testing for all currently recommended targets on the panel, the diagnostic yield would have increased to 55% (4396/8000). Ordering providers at 9/50 different contacted sites agreed to interview requests. 100% (9/9) of respondents indicated that their patients experience significant disparities in access to carrier screening, and that the primary cause of these inequities was insufficient insurance reimbursement. 67% (6/9) of respondents indicated that &gt;50% of their patient population identified as non-white and would have “very strongly” benefitted from “testing for other disorders beyond CF.”

Conclusions

Despite clinical practice guidelines urging for more population-neutral carrier screening, major gaps exist between what is recommended versus ultimately ordered. This significantly limits the clinical utility of testing, especially in patients from underrepresented backgrounds. Improved insurance coverage for more inclusive carrier screening is needed to help reduce such disparities.