The Contribution of Low-Frequency and Rare Coding Variation to Susceptibility to Type 2 Diabetes.
Coding variants
Exome
GWAS
Genetic architecture
RVAS
Rare variants
Sequencing
Journal
Current diabetes reports
ISSN: 1539-0829
Titre abrégé: Curr Diab Rep
Pays: United States
ID NLM: 101093791
Informations de publication
Date de publication:
08 04 2019
08 04 2019
Historique:
entrez:
9
4
2019
pubmed:
9
4
2019
medline:
7
2
2020
Statut:
epublish
Résumé
Soon after the first genome-wide association study (GWAS) for type 2 diabetes (T2D) was published, it was hypothesized that rare and low-frequency variants might explain a substantial proportion of disease risk. Rare coding variants in particular were emphasized given their large expected role in disease. This review summarizes the extent to which recent T2D genetic studies provide evidence for or against this hypothesis. Following a comprehensive study of T2D genetic architecture using three sequencing and genotyping technologies, four even larger studies have provided a yet higher resolution view of the role of rare and low-frequency coding variation in T2D susceptibility. Empirical evidence strongly suggests that common regulatory variants are the dominant contributor to T2D heritability. However, rare coding variants may nonetheless be pervasive across T2D-relevant genes. A strategy using common variants to map disease genes, and rare coding variants to link molecular gene perturbations to cellular and phenotypic effects, may be an effective means to investigate T2D pathogenesis and potential new therapies.
Identifiants
pubmed: 30957210
doi: 10.1007/s11892-019-1142-5
pii: 10.1007/s11892-019-1142-5
pmc: PMC6451938
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
25Références
Cell. 2010 Apr 16;141(2):210-7
pubmed: 20403315
Genet Med. 2002 Mar-Apr;4(2):45-61
pubmed: 11882781
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7
pubmed: 19474294
Diabetes. 2017 Feb;66(2):335-346
pubmed: 27899486
Nat Genet. 2016 Mar;48(3):314-7
pubmed: 26854916
Science. 2009 Apr 17;324(5925):387-9
pubmed: 19264985
Nat Rev Genet. 2011 Aug 18;12(9):628-40
pubmed: 21850043
PLoS Genet. 2015 Apr 23;11(4):e1005165
pubmed: 25906071
Diabetologia. 2010 Aug;53(8):1656-68
pubmed: 20424817
Nat Genet. 2012 Jan 29;44(3):297-301
pubmed: 22286214
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
Nat Genet. 2016 Dec;48(12):1570-1575
pubmed: 27749844
Nat Genet. 2005 Feb;37(2):161-5
pubmed: 15654334
Nature. 2009 Sep 10;461(7261):272-6
pubmed: 19684571
Nat Genet. 2014 Apr;46(4):357-63
pubmed: 24584071
Nat Rev Endocrinol. 2016 Jul;12(7):394-406
pubmed: 27080136
N Engl J Med. 2009 Apr 23;360(17):1699-701
pubmed: 19369661
Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):E455-64
pubmed: 24443550
Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14872-7
pubmed: 19706465
Nat Genet. 2011 Oct 09;43(11):1066-73
pubmed: 21983784
N Engl J Med. 2006 Mar 23;354(12):1264-72
pubmed: 16554528
Nature. 2016 Aug 4;536(7614):41-47
pubmed: 27398621
Nat Rev Genet. 2010 Jan;11(1):31-46
pubmed: 19997069
Am J Hum Genet. 2013 Dec 5;93(6):1072-86
pubmed: 24290377
Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13127-32
pubmed: 25157153
Science. 2008 Nov 7;322(5903):881-8
pubmed: 18988837
Diabetologia. 2013 Feb;56(2):298-310
pubmed: 23160641
Nat Commun. 2015 Jan 29;6:5897
pubmed: 25631608
Nat Rev Drug Discov. 2013 Aug;12(8):581-94
pubmed: 23868113
Nat Rev Genet. 2016 Sep;17(9):535-49
pubmed: 27402621
N Engl J Med. 2015 Sep 3;373(10):895-907
pubmed: 26287746
Nat Genet. 2013 Feb;45(2):197-201
pubmed: 23263489
BMC Med. 2017 Dec 6;15(1):213
pubmed: 29207974
N Engl J Med. 2009 Apr 23;360(17):1696-8
pubmed: 19369660
Genome Biol. 2016 Nov 17;17(1):233
pubmed: 27855690
Cell. 2011 Sep 30;147(1):32-43
pubmed: 21962505
Nature. 2014 Aug 14;512(7513):190-3
pubmed: 25043022
Nat Genet. 2018 Feb;50(2):172-174
pubmed: 29311636
Diabetes. 2009 Sep;58(9):2070-83
pubmed: 19542200
Nat Genet. 2008 Jun;40(6):695-701
pubmed: 18509313
Biochem J. 2009 Jul 15;421(3):371-6
pubmed: 19450229
N Engl J Med. 2012 Sep 13;367(11):1002-11
pubmed: 22970944
Hum Hered. 2008;66(1):35-49
pubmed: 18223311
Science. 2012 May 11;336(6082):740-3
pubmed: 22582263
PLoS One. 2012;7(7):e40972
pubmed: 22829903
N Engl J Med. 2012 Mar 22;366(12):1108-18
pubmed: 22435370
Nat Genet. 2012 May 29;44(6):623-30
pubmed: 22641211
J Clin Endocrinol Metab. 2014 May;99(5):E926-30
pubmed: 24471563
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3871-6
pubmed: 19202052
Nat Genet. 2003 Mar;33 Suppl:228-37
pubmed: 12610532
Am J Hum Genet. 2001 Jul;69(1):124-37
pubmed: 11404818
Nat Genet. 2012 Dec;44(12):1294-301
pubmed: 23104008
Nat Genet. 2006 Mar;38(3):320-3
pubmed: 16415884
Nat Genet. 2015 Nov;47(11):1228-35
pubmed: 26414678
Nat Genet. 2014 Mar;46(3):294-8
pubmed: 24464100
Nat Genet. 2018 Nov;50(11):1505-1513
pubmed: 30297969
Nat Genet. 2018 Apr;50(4):559-571
pubmed: 29632382
Am J Hum Genet. 2007 Apr;80(4):727-39
pubmed: 17357078
Diabetes. 2017 Jul;66(7):2019-2032
pubmed: 28341696
Nature. 2018 Oct;562(7726):217-222
pubmed: 30209399
Cell Metab. 2015 Mar 3;21(3):357-68
pubmed: 25640731
Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7642-E7649
pubmed: 30038024
JAMA. 2014 Jun 11;311(22):2305-14
pubmed: 24915262
Am J Hum Genet. 2014 Jul 3;95(1):5-23
pubmed: 24995866
Nature. 2007 Feb 22;445(7130):881-5
pubmed: 17293876
PLoS Genet. 2015 Jan 27;11(1):e1004876
pubmed: 25625282
Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):379-384
pubmed: 29279374
Hum Mutat. 2016 Mar;37(3):235-41
pubmed: 26555599
Am J Hum Genet. 2011 Jul 15;89(1):82-93
pubmed: 21737059
Nat Genet. 2013 Nov;45(11):1380-5
pubmed: 24097065
Islets. 2010 Jan-Feb;2(1):49-50
pubmed: 21099294
Science. 2012 Jul 6;337(6090):64-9
pubmed: 22604720
Nature. 2009 Oct 8;461(7265):747-53
pubmed: 19812666
Nat Rev Genet. 2010 Jun;11(6):415-25
pubmed: 20479773
Nat Genet. 2000 Sep;26(1):76-80
pubmed: 10973253
Am J Hum Genet. 2017 Sep 7;101(3):315-325
pubmed: 28886340
PLoS Biol. 2010 Jan 26;8(1):e1000294
pubmed: 20126254
Am J Hum Genet. 2012 Aug 10;91(2):224-37
pubmed: 22863193
Nat Genet. 2013 Dec;45(12):1418-27
pubmed: 24141362
Nature. 2017 Apr 12;544(7649):235-239
pubmed: 28406212
Curr Protoc Hum Genet. 2013 Jan;Chapter 7:Unit7.20
pubmed: 23315928