A Mayo Clinic study of nearly 50,000 adults found many carriers of sickle cell and beta-thalassemia traits were not identified in electronic health records, highlighting gaps in current documentation practices.
Genetic testing can identify individuals with sickle cell trait or beta-thalassemia trait whose carrier status may otherwise go unrecognized, according to a study from Mayo Clinic researchers published in Mayo Clinic Proceedings.
Using genetic sequencing data from nearly 50,000 participants, researchers identified carrier traits for sickle cell anemia and beta-thalassemia at clinically significant levels. The findings highlight how population-scale genomic screening can complement traditional newborn testing programs, provide missing diagnostic details, and support earlier family planning and reproductive counseling.
“If we can identify carrier status earlier, we have more opportunities for reproductive counseling, appropriate preventive care and helping patients understand what these findings may mean for their families,” says Nathaniel Miller, MD, a Mayo Clinic family medicine physician and first author of the study, in a release.
Discrepancies Between Genomic Findings and Medical Records
Sickle cell anemia and beta-thalassemia are inherited hemoglobinopathies that alter hemoglobin production and red blood cell function. Individuals carrying sickle cell trait or beta-thalassemia trait typically present with few or no clinical symptoms, but they can pass these pathogenic variants to their children.
The study evaluated genomic data generated through Tapestry, a Mayo Clinic initiative that enrolled more than 98,000 participants between July 2020 and May 2024 to produce whole exome sequencing data for clinical care, genomic education, and research discovery. Investigators evaluated exome sequencing results from nearly 50,000 individuals for pathogenic variants linked to sickle cell trait and beta-thalassemia trait, comparing those results directly with diagnostic codes in the participants’ electronic health records.
The comparison uncovered significant diagnostic gaps:
- Among 116 participants identified via genetic testing as having sickle cell trait, only 19 had a corresponding diagnosis code in their medical records.
- Among 98 participants identified as beta-thalassemia carriers, only 47 had a corresponding diagnosis code.
Researchers also observed discordances in which existing diagnosis codes did not align with genetic sequencing findings. The study authors noted that these discrepancies underscore the need for further research, as they may stem from historical screening limitations, classification differences, and varied clinical documentation practices.
Addressing Gaps in Historical Screening
While all US states now perform universal newborn screening for major hemoglobinopathies such as sickle cell disease, historical protocols for identifying and reporting carrier status have varied widely, particularly regarding thalassemias. In addition, older adult cohorts were born before widespread newborn screening programs were established.
The study authors indicated that these findings demonstrate the clinical utility of secondary genomic screening in adulthood to capture hereditary risk factors that standard screening missed or failed to document. The data also highlight an opportunity to establish standardized clinical laboratory guidance on reporting carrier traits and coordinating downstream genetic counseling.
“From a primary care and population health perspective, the goal is to identify carrier status early, ideally before pregnancy, because many people don’t know they are carriers,” says Isa Houwink, MD, PhD, a Mayo Clinic family medicine physician and senior author of the study, in a release. “That creates an important opportunity for preconception counseling and informed family planning.”
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