Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions

Aaron C Miller; Alejandro P Comellas; Douglas B Hornick; David A Stoltz; Joseph E Cavanaugh; Alicia K Gerke; Michael J Welsh; Joseph Zabner; Philip M Polgreen

doi:10.1073/pnas.1914912117

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Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions

Journal article

Open access

Peer reviewed

Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions

Aaron C Miller, Alejandro P Comellas, Douglas B Hornick, David A Stoltz, Joseph E Cavanaugh, Alicia K Gerke, Michael J Welsh, Joseph Zabner and Philip M Polgreen

Proceedings of the National Academy of Sciences - PNAS, Vol.117(3), pp.1621-1627

01/21/2020

DOI: 10.1073/pnas.1914912117

PMCID: PMC6983448

PMID: 31882447

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Abstract

Autosomal recessive diseases, such as cystic fibrosis (CF), require inheritance of 2 mutated genes. However, some studies indicate that CF carriers are at increased risk for some conditions associated with CF. These investigations focused on single conditions and included small numbers of subjects. Our goal was to determine whether CF carriers are at increased risk for a range of CF-related conditions. Using the Truven Health MarketScan Commercial Claims database (2001-2017), we performed a population-based retrospective matched-cohort study. We identified 19,802 CF carriers and matched each carrier with 5 controls. The prevalence of 59 CF-related diagnostic conditions was evaluated in each cohort. Odds ratios for each condition were computed for CF carriers relative to controls. All 59 CF-related conditions were more prevalent among carriers compared with controls, with significantly increased risk ( < 0.05) for 57 conditions. Risk was increased for some conditions previously linked to CF carriers (e.g., pancreatitis, male infertility, bronchiectasis), as well as some conditions not previously reported (e.g., diabetes, constipation, cholelithiasis, short stature, failure to thrive). We compared our results with 23,557 subjects with CF, who were also matched with controls; as the relative odds of a given condition increased among subjects with CF, so did the corresponding relative odds for carriers ( < 0.001). Although individual-level risk remained low for most conditions, because there are more than 10 million carriers in the US, population-level morbidity attributable to the CF carrier state is likely substantial. Genetic testing may inform prevention, diagnosis, and treatment for a broad range of CF carrier-related conditions.

Adolescent

Adult

Child

Child, Preschool

Cystic Fibrosis - epidemiology

Cystic Fibrosis - genetics

Female

Genetic Carrier Screening

Genetic Testing

Heterozygote

Humans

Infant

Infant, Newborn

Male

Middle Aged

Molecular Epidemiology

Mutation

Prevalence

Retrospective Studies

United States

Young Adult

Details

Title: Subtitle: Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions
Creators: Aaron C Miller - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242
Alejandro P Comellas - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Douglas B Hornick - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
David A Stoltz - Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242
Joseph E Cavanaugh - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242
Alicia K Gerke - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Michael J Welsh - Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242
Joseph Zabner - Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Philip M Polgreen - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.117(3), pp.1621-1627
DOI: 10.1073/pnas.1914912117
PMID: 31882447
PMCID: PMC6983448
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Grant note: P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS UL1 TR002537 / NCATS NIH HHS Howard Hughes Medical Institute P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 01/21/2020
Academic Unit: Neurology; Infectious Diseases; ICTS; Biostatistics; Injury Prevention Research Center; Statistics and Actuarial Science; Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Epidemiology; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
Record Identifier: 9984214940902771

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