{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:21:13Z","timestamp":1793146873959,"version":"4.5.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"3","license":[{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["HL091842"],"award-info":[{"award-number":["HL091842"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR002537"],"award-info":[{"award-number":["UL1TR002537"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["R458CR07"],"award-info":[{"award-number":["R458CR07"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,1,21]]},"abstract":"<jats:p>\n                    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\u20132017), 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 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 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 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1914912117","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T17:55:11Z","timestamp":1577469311000},"page":"1621-1627","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":191,"title":["Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions"],"prefix":"10.1073","volume":"117","author":[{"given":"Aaron C.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro P.","family":"Comellas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B.","family":"Hornick","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stoltz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Cavanaugh","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia K.","family":"Gerke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Zabner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Polgreen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242;"},{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,12,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic fibrosis","volume":"388","author":"Elborn J. S.","year":"2016","unstructured":"J. S. Elborn, Cystic fibrosis. 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Chest 130, 1441\u20131447 (2006).","journal-title":"Chest"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/S0140-6736(03)13368-5","article-title":"Effect of genotype on phenotype and mortality in cystic fibrosis: A retrospective cohort study","volume":"361","author":"McKone E. F.","year":"2003","unstructured":"E. F. McKone, S. S. Emerson, K. L. Edwards, M. L. Aitken, Effect of genotype on phenotype and mortality in cystic fibrosis: A retrospective cohort study. Lancet 361, 1671\u20131676 (2003).","journal-title":"Lancet"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1097\/GIM.0b013e31818e55a2","article-title":"Clinical practice and genetic counseling for cystic fibrosis and CFTR-related disorders","volume":"10","author":"Moskowitz S. M.","year":"2008","unstructured":"S. M. Moskowitz ., Clinical practice and genetic counseling for cystic fibrosis and CFTR-related disorders. Genet. 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