A novel splice-affecting
Journal
The Lancet regional health. Europe
ISSN: 2666-7762
Titre abrégé: Lancet Reg Health Eur
Pays: England
ID NLM: 101777707
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
received:
18
07
2022
revised:
15
09
2022
accepted:
03
10
2022
entrez:
17
1
2023
pubmed:
18
1
2023
medline:
18
1
2023
Statut:
epublish
Résumé
The genetic disease architecture of Inuit includes a large number of common high-impact variants. Identification of such variants contributes to our understanding of the genetic aetiology of diseases and improves global equity in genomic personalised medicine. We aimed to identify and characterise novel variants in genes associated with Maturity Onset Diabetes of the Young (MODY) in the Greenlandic population. Using combined data from Greenlandic population cohorts of 4497 individuals, including 448 whole genome sequenced individuals, we screened 14 known MODY genes for previously identified and novel variants. We functionally characterised an identified novel variant and assessed its association with diabetes prevalence and cardiometabolic traits and population impact. We identified a novel variant in the known MODY gene The reported variant has the largest population impact of any previously reported variant within a MODY gene. Together with the recessive Novo Nordisk Foundation, Independent Research Fund Denmark, and Karen Elise Jensen's Foundation.
Sections du résumé
Background
UNASSIGNED
The genetic disease architecture of Inuit includes a large number of common high-impact variants. Identification of such variants contributes to our understanding of the genetic aetiology of diseases and improves global equity in genomic personalised medicine. We aimed to identify and characterise novel variants in genes associated with Maturity Onset Diabetes of the Young (MODY) in the Greenlandic population.
Methods
UNASSIGNED
Using combined data from Greenlandic population cohorts of 4497 individuals, including 448 whole genome sequenced individuals, we screened 14 known MODY genes for previously identified and novel variants. We functionally characterised an identified novel variant and assessed its association with diabetes prevalence and cardiometabolic traits and population impact.
Findings
UNASSIGNED
We identified a novel variant in the known MODY gene
Interpretation
UNASSIGNED
The reported variant has the largest population impact of any previously reported variant within a MODY gene. Together with the recessive
Funding
UNASSIGNED
Novo Nordisk Foundation, Independent Research Fund Denmark, and Karen Elise Jensen's Foundation.
Identifiants
pubmed: 36649380
doi: 10.1016/j.lanepe.2022.100529
pii: S2666-7762(22)00225-3
pmc: PMC9832271
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100529Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
AT has received funding from the 10.13039/501100009708Novo Nordisk Foundation NNF17OC0028328. AA and ZL have received funding from the 10.13039/501100009708Novo Nordisk Foundation (NNF20OC0061343). NG has received funding from the 10.13039/501100009708Novo Nordisk Foundation (NNF16OC0019986). IM has received funding from a Villum Young Investigator grant (19114). MEJ has received research grants from 10.13039/100004325AstraZeneca, 10.13039/100019944Sanofi Aventis, 10.13039/100002429AMGEN, 10.13039/100001003Boehringer Ingelheim and Novo Nordisk A/S. FFS has received funding from the 10.13039/501100001734University of Copenhagen. The population surveys of Greenland were funded by the Department of Health, Greenland, The 10.13039/501100009708Novo Nordisk Foundation (NNF17OC0028136 & NNF17SH0027192), The 10.13039/501100004836Independent Research Fund Denmark, and 10.13039/501100004046Karen Elise Jensen's Foundation. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the 10.13039/501100009708Novo Nordisk Foundation (NNF18CC0034900). None of the funding agencies had any role in study design or collection, analysis, or interpretation of data. The authors have no further conflicts of interest to declare.
Références
Curr Biol. 2021 May 24;31(10):2214-2219.e4
pubmed: 33711251
J Clin Invest. 1967 Mar;46(3):323-35
pubmed: 6023769
Methods Mol Biol. 2010;653:249-57
pubmed: 20721748
JAMA. 2014 Jun 11;311(22):2305-14
pubmed: 24915262
Diabetologia. 1985 Jul;28(7):412-9
pubmed: 3899825
Diabetes Care. 2021 Dec;44(12):2673-2682
pubmed: 34607834
Am J Hum Genet. 2013 Aug 8;93(2):278-88
pubmed: 23910464
Am J Hum Genet. 2015 Jan 8;96(1):54-69
pubmed: 25557782
Bioinformatics. 2016 Feb 15;32(4):590-2
pubmed: 26500154
Diabetes Care. 2018 Aug;41(8):1726-1731
pubmed: 29844095
Diabetes. 2014 Aug;63(8):2838-44
pubmed: 24677712
Nat Metab. 2020 Oct;2(10):1126-1134
pubmed: 33046911
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4614-9
pubmed: 11904371
Am J Hum Genet. 2016 Apr 7;98(4):653-66
pubmed: 27018471
Nat Genet. 2014 Apr;46(4):357-63
pubmed: 24584071
Diabet Med. 2000 Jul;17(7):543-5
pubmed: 10972586
Genetics. 2017 Feb;205(2):787-801
pubmed: 27903613
Nature. 2010 Feb 11;463(7282):757-62
pubmed: 20148029
Nature. 2020 Jun;582(7811):240-245
pubmed: 32499647
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Nature. 2016 Aug 4;536(7614):41-47
pubmed: 27398621
Nature. 2019 Dec;576(7785):106-111
pubmed: 31802016
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
J Clin Endocrinol Metab. 1999 Mar;84(3):1077-82
pubmed: 10084598
Hum Mutat. 2013 May;34(5):669-85
pubmed: 23348805
Diabetes Care. 2002 Dec;25(12):2292-301
pubmed: 12453976
Nature. 2021 Nov;599(7886):628-634
pubmed: 34662886
Diabetologia. 2022 May;65(5):912
pubmed: 35238956
Nature. 2019 Jun;570(7760):182-188
pubmed: 31168093
Nat Genet. 2012 Jun 17;44(7):821-4
pubmed: 22706312
Science. 2014 Aug 29;345(6200):1255832
pubmed: 25170159
Diabetes. 2017 Feb;66(2):335-346
pubmed: 27899486
Science. 2020 Mar 20;367(6484):
pubmed: 32193295
Nature. 2014 Aug 14;512(7513):190-3
pubmed: 25043022
Nat Genet. 2018 Feb;50(2):172-174
pubmed: 29311636
Diabetes Care. 2004 May;27(5):1102-7
pubmed: 15111528
Sci Rep. 2018 Aug 24;8(1):12780
pubmed: 30143652
Clin Chem. 1972 Jun;18(6):499-502
pubmed: 4337382
Nat Genet. 2006 Feb;38(2):209-13
pubmed: 16415888
Nature. 2016 Oct 13;538(7624):201-206
pubmed: 27654912
Bioinformatics. 2011 Aug 1;27(15):2156-8
pubmed: 21653522
Diabetes. 2001 Nov;50(11):2472-80
pubmed: 11679424
Diabetes. 1997 May;46(5):912-6
pubmed: 9133564
Diabetes Care. 1999 Sep;22(9):1462-70
pubmed: 10480510
Nature. 2014 Feb 6;506(7486):97-101
pubmed: 24390345
J Clin Invest. 1994 Sep;94(3):1196-204
pubmed: 8083360
Nat Genet. 2014 Mar;46(3):294-8
pubmed: 24464100
Nat Genet. 2018 Nov;50(11):1505-1513
pubmed: 30297969
Nat Genet. 2020 Jul;52(7):680-691
pubmed: 32541925
Diabetes. 2002 Aug;51(8):2355-62
pubmed: 12145145
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Diabetes Care. 2002 Dec;25(12):2287-91
pubmed: 12453975
Diabetes Res Clin Pract. 2000 Mar;47(3):177-84
pubmed: 10741566
Genes (Basel). 2013 Sep 26;4(4):522-35
pubmed: 24705260
EMBO J. 2000 Aug 15;19(16):4257-64
pubmed: 10944108
Diabetes Res Clin Pract. 2010 Jan;87(1):4-14
pubmed: 19896746
Diabet Med. 2016 Jul;33(7):976-84
pubmed: 26479152
Diabetes Care. 2020 Jul;43(7):1617-1635
pubmed: 32561617
Nat Genet. 2013 Nov;45(11):1380-5
pubmed: 24097065
Diabetes. 2003 Aug;52(8):2182-6
pubmed: 12882939
Genome Res. 2009 Sep;19(9):1655-64
pubmed: 19648217
Diabetes Care. 2003 Nov;26(11):3191-2
pubmed: 14578267
Genome Res. 2017 Jan;27(1):1-14
pubmed: 27965293
Cell. 2018 Nov 15;175(5):1185-1197.e22
pubmed: 30415837
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Diabetes. 2015 Dec;64(12):4322-32
pubmed: 26246406
Diabetes. 2009 May;58(5):1212-21
pubmed: 19223598
Diabetes Care. 2005 Jul;28(7):1751-6
pubmed: 15983330
Diabetologia. 2018 Sep;61(9):2005-2015
pubmed: 29926116
Science. 2018 Jun 29;360(6396):
pubmed: 29743352
Int J Circumpolar Health. 2003;62 Suppl 1:3-79
pubmed: 14527126