# Beyond Carrier Status: CFTR Heterozygosity as an Overlooked Clinical Risk Factor for Pancreatitis

## TL;DR

This study shows that being a carrier of a CFTR gene variant increases the risk of pancreatitis in women, but this risk is often overlooked in clinical practice.

## Contribution

The study identifies CFTR heterozygosity as a novel clinical risk factor for pancreatitis that is not widely recognized.

## Key findings

- CFTR carriers had a 4.68 times higher risk of acute pancreatitis compared to non-carriers.
- CFTR carrier status was not clinically linked to pancreatitis diagnoses in medical records.
- Integrating carrier screening results into EHRs could improve early diagnosis and personalized care.

## Abstract

This study assessed the effect of CFTR pathogenic variant status, detected during prenatal carrier screening, for the incidence and clinical recognition of cystic fibrosis‐related phenotypes. Data were queried from the Vanderbilt University Medical Center clinical genetic database (CGdb), which includes clinically reported pathogenic variants and electronic health records (EHRs) from 2001 to 2023. Based on carrier screening results, we identified individuals heterozygous for a pathogenic CFTR variant and those who tested negative. Logistic regression tested associations between CFTR carrier status and 11 cystic fibrosis (CF)‐related phenotypes. A phenome‐wide association study (PheWAS) was performed to identify additional phenotypic associations, and manual chart review was conducted to evaluate recognition and clinical application of CFTR carrier status in patients diagnosed with pancreatitis. Among 12,082 women tested, CFTR carriers (n = 451) were at significantly higher risk of developing acute pancreatitis (p = 3.93 × 10−6; OR = 4.68 [2.43–9.00]). No other CF‐related phenotypes were significantly associated in this female cohort. Manual chart review revealed that CFTR carrier screening results were not clinically correlated with pancreatitis diagnoses. In this large cohort of women tested for prenatal carrier screening, CFTR pathogenic variants relevant to pancreatitis were overlooked, despite informing etiology, management, and prognosis.

CFTR carrier status detected via prenatal screening is associated with increased pancreatitis risk in women, but clinical recognition remains low. Integrating carrier results into electronic health records may enhance personalized care and aid in early diagnosis.