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Genome Database Analysis Suggests Cystic Fibrosis is More Globally Distributed Than Previously Believed

Genome Database Analysis Suggests Cystic Fibrosis is More Globally Distributed Than Previously Believed 1024 768 Katie Brind'Amour, PhD, MS, CHES

Despite lower CF incidence in non-European populations, total CF births in Asia, Africa and South America likely equal or surpass those in North America and Europe.

Cystic fibrosis (CF) has long been viewed as a disease that primarily affects people of European descent. Even as genetic research expanded and highly effective modulator therapies (HEMT) became available, registry data continued to suggest that CF was exceedingly rare in much of Asia, Africa and South America. Now, a study analyzing more than 800,000 genomes and exomes challenges that assumption, indicating that these regions may produce as many or more CF‑affected infants each year as North America and Europe.

portrait of Sriram Vaidyanathan, PhD

Sriram Vaidyanathan, PhD

“Traditionally, CF literature tried to characterize global incidence using immigrant populations living in North America and the United Kingdom, and often those registries included only a few hundred people from a handful of countries,” explains Sriram Vaidyanathan, PhD, principal investigator in the Jerry R. Mendell Center for Gene Therapy at Nationwide Children’s Hospital and senior author on the genome-based publication. “It’s hard to extrapolate from 400 people for a continent containing half the world’s population. We wanted to get a more representative sampling by country.”

To achieve that, Vaidyanathan and his colleagues turned to gnomAD, a publicly available genomic database containing sequence data from 25 countries. By identifying all pathogenic CFTR variants present in each ancestry group and applying Hardy-Weinberg principles, the team generated population‑specific incidence estimates.

Their findings generally aligned with historic registry data: Europeans show the highest CF incidence, at 44-52 CF cases per 100,000 births, followed by Latino/Admixed Americans at 11-14, African/African Americans at 7, South Asians at 6, Middle Eastern at 4 and East Asians at 0.2-1 CF cases per 100,000 births.

Despite improving insight into global incidence, Dr. Vaidyanathan felt the per-birth rate did not tell the whole CF story.

When the team translated the incidence rates into absolute annual births using United Nations population data, the distribution of disease burden shifted substantially. Countries with lower CF incidence but far higher birth rates likely produce large numbers of affected infants; the study estimated about 1,582 annual CF births in India, 700 in Nigeria, 390 in Brazil and 196 in China, compared with approximately 1,190 in the United States and 300 in the United Kingdom.

The fact that the genomic data captured all known variants — not just those detected by newborn screening panels — also allowed the team to explore the frequency of different CF-causing mutations in the CFTR gene across populations.

F508del is the most common CF variant in European populations, present in ~65% of cases, but was confirmed as far less common among patients of other ancestries, ranging from 9% in East Asians to 27-33% in African/African American, South Asian and Middle Eastern groups. The broad genetic variation present also indicated that a substantial percentage of pathogenic alleles — more than 70% in some populations — would be missed by common U.S. newborn screening panels.

“Panel‑based screening was designed around variants common in Europeans, so it can miss a large fraction of disease‑causing alleles in other groups,” says Dr. Vaidyanathan, whose team cross-checked the variants found in each ancestry group against the ones included in four different panels. “The Wisconsin panel does better than most, but the only truly comprehensive approach is full‑gene CFTR sequencing.”

The team also found that many people with CF in other countries would not be eligible for treatment using current HEMT drugs, since 24-60% of non-European CF cases would have disease caused by pathogenic alleles not impacted by those drugs, depending on the population.

Together, the study data suggest that many patients of non-European ancestry may be missed by current screening tools, and that even once identified, many cannot benefit from disease-modifying therapies. It is Dr. Vaidyanathan’s hope that understanding the large number of patients globally with CF — and their need for novel therapies — can motivate policymakers and pharmaceutical companies to invest in CF infrastructure to help diagnose and treat these patients.

The findings also have implications for patient management, especially since non-European populations now account for about half of the annual births in the US.

“CF can affect anybody, regardless of race or ethnicity or ancestry,” Dr. Vaidyanathan reminds families and clinicians. “If you think the phenotype fits CF, consider CF. And when considering results from prenatal or newborn screening, consider whether it’s a true negative or whether the result could be skewed by the type of test used.”

Dr. Vaidyanathan began exploring global CF incidence to increase understanding of disease burden in regions without established CF registries, screening programs, or diagnostic resources, but the insight into variant distribution also reinforces his broader approach to gene therapy.

“My work is centered on the idea of replacing the whole gene so that we don’t have to worry about what individual mutation is present, in the hopes that the therapy might help the most people,” Dr. Vaidyanathan says.

 

Reference:

Bar L, Darrah RJ, Vaidyanathan S. Analysis of the Genome Aggregation Database (gnomAD) reveals a global burden of cystic fibrosis and the need for improved diagnosis and care. eBioMedicine. 2026;124:106145. doi:10.1016/j.ebiom.2026.106145.

Image credit: Adobe Stock (header); Nationwide Children’s (portrait)

About the author

Katherine (Katie) Brind’Amour is a freelance medical and health science writer based in Pennsylvania. She has written about nearly every therapeutic area for patients, doctors and the general public. Dr. Brind’Amour specializes in health literacy and patient education. She completed her BS and MS degrees in Biology at Arizona State University and her PhD in Health Services Management and Policy at The Ohio State University. She is a Certified Health Education Specialist and is interested in health promotion via health programs and the communication of medical information.

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