-
Tytuł:
-
Cystic fibrosis-related diabetes onset can be predicted using biomarkers measured at birth.
-
Autorzy:
-
Lin YC; Department of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Keenan K; Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Gong J; Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Panjwani N; Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Avolio J; Program in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Lin F; Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Adam D; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.; CRCHUM, Montréal, QC, Canada.
Barrett P; IWK Health Centre, Halifax, NS, Canada.
Bégin S; CRCHUM, Montréal, QC, Canada.
Berthiaume Y; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
Bilodeau L; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, Québec City, QC, Canada.
Bjornson C; Alberta Children's Hospital, Calgary, AB, Canada.
Brusky J; Jim Pattison Children's Hospital, Saskatoon, SK, Canada.
Burgess C; British Columbia Children's Hospital, Vancouver, BC, Canada.
Chilvers M; British Columbia Children's Hospital, Vancouver, BC, Canada.
Consunji-Araneta R; The Children's Hospital of Winnipeg, Winnipeg, MB, Canada.
Côté-Maurais G; CRCHUM, Montréal, QC, Canada.
Dale A; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
Donnelly C; IWK Health Centre, Halifax, NS, Canada.
Fairservice L; Alberta Children's Hospital, Calgary, AB, Canada.
Griffin K; St. Michael's Hospital, Toronto, ON, Canada.
Henderson N; Kingston Health Sciences Centre, Kingston, ON, Canada.
Hillaby A; University of Alberta Hospital, Edmonton, AB, Canada.
Hughes D; IWK Health Centre, Halifax, NS, Canada.
Iqbal S; The Children's Hospital of Winnipeg, Winnipeg, MB, Canada.
Itterman J; The Children's Hospital of Western Ontario, London, ON, Canada.
Jackson M; Royal University Hospital, Saskatoon, SK, Canada.
Karlsen E; St. Paul's Hospital, Vancouver, BC, Canada.
Kosteniuk L; Royal University Hospital, Saskatoon, SK, Canada.
Lazosky L; St. Paul's Hospital, Vancouver, BC, Canada.
Leung W; University of Alberta Hospital, Edmonton, AB, Canada.
Levesque V; Foothills Medical Centre, Calgary, AB, Canada.
Maille É; CRCHUM, Montréal, QC, Canada.
Mateos-Corral D; IWK Health Centre, Halifax, NS, Canada.
McMahon V; British Columbia Children's Hospital, Vancouver, BC, Canada.
Merjaneh M; CRCHUM, Montréal, QC, Canada.
Morrison N; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
Parkins M; Foothills Medical Centre, Calgary, AB, Canada.
Pike J; St. Michael's Hospital, Toronto, ON, Canada.
Price A; The Children's Hospital of Western Ontario, London, ON, Canada.
Quon BS; St. Paul's Hospital, Vancouver, BC, Canada.
Reisman J; The Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
Smith C; Foothills Medical Centre, Calgary, AB, Canada.
Smith MJ; Janeway Children's Health & Rehabilitation Centre, St. John's, NL, Canada.
Vadeboncoeur N; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, Québec City, QC, Canada.
Veniott D; St. Mary's General Hospital, Kitchener, ON, Canada.
Viczko T; British Columbia Children's Hospital, Vancouver, BC, Canada.
Wilcox P; St. Paul's Hospital, Vancouver, BC, Canada.
van Wylick R; Kingston Health Sciences Centre, Kingston, ON, Canada.
Cutting G; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tullis E; St. Michael's Hospital, Toronto, ON, Canada.
Ratjen F; Program in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.; Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada.
Rommens JM; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Sun L; Department of Statistical Sciences, University of Toronto, Toronto, ON, Canada.
Solomon M; Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada.
Stephenson AL; St. Michael's Hospital, Toronto, ON, Canada.
Brochiero E; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.; CRCHUM, Montréal, QC, Canada.
Blackman S; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Corvol H; Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Pediatric Pulmonary Department, Paris, France.; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Saint Antoine, Paris, France.
Strug LJ; Department of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. .; Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada. .; Department of Statistical Sciences, University of Toronto, Toronto, ON, Canada. .; The Center for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada. .; Department of Computer Science, University of Toronto, Toronto, ON, Canada. .
-
Źródło:
-
Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2021 May; Vol. 23 (5), pp. 927-933. Date of Electronic Publication: 2021 Jan 26.
-
Typ publikacji:
-
Journal Article; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Publication: 2022- : [New York] : Elsevier
Original Publication: Baltimore, MD : Lippincott, Williams & Wilkins, c1998-
-
MeSH Terms:
-
Cystic Fibrosis*/complications
Cystic Fibrosis*/diagnosis
Cystic Fibrosis*/genetics
Diabetes Mellitus*/epidemiology
Diabetes Mellitus*/genetics
Biomarkers ; Canada ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Genome-Wide Association Study ; Humans ; Infant, Newborn
-
References:
-
J Clin Endocrinol Metab. 2020 May 1;105(5):. (PMID: 31697830)
Mutagenesis. 2013 Jan;28(1):25-37. (PMID: 23188737)
Am J Hum Genet. 2015 Jul 2;97(1):125-38. (PMID: 26140448)
Diabetes Care. 2010 Dec;33(12):2697-708. (PMID: 21115772)
Diabetes Care. 2008 Sep;31(9):1789-94. (PMID: 18535191)
PLoS Genet. 2013 Mar;9(3):e1003348. (PMID: 23555274)
J Cyst Fibros. 2020 Mar;19(2):316-320. (PMID: 31439463)
Diabetes Res Clin Pract. 1999 Aug;45(1):61-73. (PMID: 10499886)
Diabetes. 2013 Oct;62(10):3627-35. (PMID: 23670970)
Diabetes. 2014 Jun;63(6):2114-9. (PMID: 24550193)
J Cyst Fibros. 2018 Mar;17(2):271-275. (PMID: 29249670)
Gastroenterology. 2011 Jan;140(1):153-61. (PMID: 20923678)
J Cyst Fibros. 2020 Jan;19(1):68-79. (PMID: 31196670)
J Pathol. 2016 Jan;238(2):311-20. (PMID: 26365583)
J Cyst Fibros. 2014 Jul;13(4):384-90. (PMID: 24513262)
J Cyst Fibros. 2016 Nov;15(6):839-845. (PMID: 27139162)
Hum Genet. 2011 May;129(5):545-52. (PMID: 21246217)
Diabetes Care. 2009 Sep;32(9):1626-31. (PMID: 19542209)
Genet Epidemiol. 2009 Jul;33(5):453-62. (PMID: 19140131)
Am J Respir Crit Care Med. 2015 Jan 15;191(2):194-200. (PMID: 25479583)
Eur Respir Rev. 2020 Mar 20;29(155):. (PMID: 32198216)
Presse Med. 2017 Jun;46(6 Pt 2):e87-e95. (PMID: 28554720)
Diabetol Metab Syndr. 2014 Apr 03;6(1):50. (PMID: 24694251)
PLoS Genet. 2019 Feb 26;15(2):e1008007. (PMID: 30807572)
Nature. 2009 Aug 6;460(7256):748-52. (PMID: 19571811)
Front Genet. 2018 May 22;9:177. (PMID: 29872446)
Int J Health Care Qual Assur. 2015;28(5):441-51. (PMID: 26020427)
Bioinformatics. 2016 Jan 1;32(1):50-7. (PMID: 26382192)
Nat Genet. 2012 May;44(5):562-9. (PMID: 22466613)
Bioinformatics. 2010 Nov 15;26(22):2867-73. (PMID: 20926424)
Nucleic Acids Res. 2014 Jan;42(Database issue):D1001-6. (PMID: 24316577)
Genome Res. 2007 Oct;17(10):1520-8. (PMID: 17785532)
Nat Protoc. 2020 Sep;15(9):2759-2772. (PMID: 32709988)
Nat Commun. 2015 Sep 29;6:8382. (PMID: 26417704)
-
Grant Information:
-
MOP 258916 Canada CIHR; MOP 117978 Canada CIHR; MOP 388348 Canada CIHR; MOP167282 Canada CIHR
-
Substance Nomenclature:
-
0 (Biomarkers)
126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
-
Entry Date(s):
-
Date Created: 20210127 Date Completed: 20210603 Latest Revision: 20220210
-
Update Code:
-
20240105
-
PubMed Central ID:
-
PMC8105168
-
DOI:
-
10.1038/s41436-020-01073-x
-
PMID:
-
33500570
-
Purpose: Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes.
Methods: Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies.
Results: The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies.
Conclusion: We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.
Erratum in: Genet Med. 2021 Nov;23(11):2235-2236. (PMID: 34389817)
