Cystic fibrosis carrier screening is missing a substantial number of at-risk individuals in non-European ancestry groups, according to a new study published in the Journal of Cystic Fibrosis. The research finds that commonly used CFTR gene testing panels are increasingly out of step with global population diversity.
CF is caused by pathogenic variants in the CFTR gene, disrupting chloride transport and leading to progressive multi-system disease. While it occurs across all ancestries, incidence has historically been highest in Northern European populations. Most carrier screening programs rely on targeted variant panels designed around variants common in people of European ancestry, limiting detection in other groups.
Using Australian registry data and international modeling, researchers found clear disparities in screening sensitivity. Panels capturing 25 to 50 variants initially identified 92 to 95% of CFTR variants in Australia, but performance dropped to 87 to 92% as population demographics shifted. International data showed detection rates of 84 to 90% in individuals of European ancestry, compared with 25 to 69% in Asian populations, 62 to 91% in Black populations, 51 to 55% in Middle Eastern groups, and just 17 to 33% in Pacific Islander groups.
The analysis indicates that achieving equitable sensitivity across ancestries would require at least 176 pan-ancestry variants, many not included in current guideline panels. The study supports transitioning toward CFTR gene sequencing to better capture global variant diversity and reduce inequities in carrier detection.
Clinically, the results suggest that screening strategies calibrated to European populations may no longer meet equity goals in increasingly diverse healthcare systems.