Genetic risk for dengue hemorrhagic fever and dengue fever in multiple ancestries.
Ancestry
Dengue
GWAS
Genetics
Risk
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
08
08
2019
revised:
28
10
2019
accepted:
26
11
2019
pubmed:
7
1
2020
medline:
2
10
2020
entrez:
6
1
2020
Statut:
ppublish
Résumé
Genetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations. We conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin American, South Asian, and South East Asian ancestries. We then developed a weighted polygenic risk score (PRS) for each participant in each of the validation cohorts of the three ancestries to predict the risk of DHF/DSS compared to DF, DHF/DSS compared to controls, and, DF compared to controls. The risk of DHF/DSS was significantly increased, odds ratio [OR] 1.84 (95%CI 1.47 to 2.31) (195 SNPs), compared to DF, fourth PRS quartile versus first quartile, in the validation cohort. The risk of DHF/DSS compared to controls was increased (OR=3.94; 95% CI 2.84 to 5.45) (278 SNPs), as was the risk of DF compared to controls (OR=1.97; 95%CI 1.63 to 2.39) (251 SNPs). Risk increased in a dose-dependent manner with increase in quartiles of PRS across comparisons. Significant associations persisted for PRS built within ancestries and applied to the same or different ancestries as well as for PRS built for one outcome (DHF/DSS or DF) and applied to the other. There is a strong genetic effect that predisposes to risk of DHF/DSS and DF. The genetic risk for DHF/DSS is higher than that for DF when compared to controls, and this effect persists across multiple ancestries.
Sections du résumé
BACKGROUND
BACKGROUND
Genetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations.
METHODS
METHODS
We conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin American, South Asian, and South East Asian ancestries. We then developed a weighted polygenic risk score (PRS) for each participant in each of the validation cohorts of the three ancestries to predict the risk of DHF/DSS compared to DF, DHF/DSS compared to controls, and, DF compared to controls.
FINDINGS
RESULTS
The risk of DHF/DSS was significantly increased, odds ratio [OR] 1.84 (95%CI 1.47 to 2.31) (195 SNPs), compared to DF, fourth PRS quartile versus first quartile, in the validation cohort. The risk of DHF/DSS compared to controls was increased (OR=3.94; 95% CI 2.84 to 5.45) (278 SNPs), as was the risk of DF compared to controls (OR=1.97; 95%CI 1.63 to 2.39) (251 SNPs). Risk increased in a dose-dependent manner with increase in quartiles of PRS across comparisons. Significant associations persisted for PRS built within ancestries and applied to the same or different ancestries as well as for PRS built for one outcome (DHF/DSS or DF) and applied to the other.
INTERPRETATION
CONCLUSIONS
There is a strong genetic effect that predisposes to risk of DHF/DSS and DF. The genetic risk for DHF/DSS is higher than that for DF when compared to controls, and this effect persists across multiple ancestries.
Identifiants
pubmed: 31901861
pii: S2352-3964(19)30794-7
doi: 10.1016/j.ebiom.2019.11.045
pmc: PMC6940652
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102584Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201000026C
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest Dr. Pare reports other from Amgen, other from Sanofi, outside the submitted work; the other authors have no conflicts of interest.
Références
J Infect Dis. 2000 Jan;181(1):2-9
pubmed: 10608744
Am J Trop Med Hyg. 1980 Jul;29(4):638-42
pubmed: 6157332
BMC Med Genet. 2014 May 17;15:58
pubmed: 24884822
BMC Genet. 2005 Apr 08;6:18
pubmed: 15819990
Acta Trop. 2018 Jan;177:186-193
pubmed: 29054571
Methods Mol Biol. 2014;1138:27-39
pubmed: 24696329
PLoS One. 2011;6(11):e27252
pubmed: 22096543
PLoS Pathog. 2017 Feb 27;13(2):e1006220
pubmed: 28241052
J Clin Microbiol. 1992 Mar;30(3):545-51
pubmed: 1372617
Microbes Infect. 2009 Feb;11(2):143-56
pubmed: 19121645
Nat Genet. 2011 Oct 16;43(11):1139-41
pubmed: 22001756
PLoS One. 2013;8(3):e59067
pubmed: 23536857
Viral Immunol. 2017 Oct;30(8):615-621
pubmed: 28650708
Am J Trop Med Hyg. 2002 Jul;67(1):102-6
pubmed: 12363051
Nat Rev Genet. 2008 Apr;9(4):255-66
pubmed: 18319743
BMC Med Genet. 2016 Jul 11;17(1):43
pubmed: 27401010
J Infect Dis. 1997 Aug;176(2):322-30
pubmed: 9237696
Clin Microbiol Rev. 1998 Jul;11(3):480-96
pubmed: 9665979
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
J Infect Dis. 2009 May 15;199(10):1442-8
pubmed: 19392621
Nat Genet. 2012 Oct;44(10):1166-70
pubmed: 22983301
Science. 2017 Nov 17;358(6365):929-932
pubmed: 29097492
Infect Genet Evol. 2017 Dec;56:99-110
pubmed: 29133029
Semin Immunol. 1992 Apr;4(2):121-7
pubmed: 1617166
Trop Med Int Health. 2006 Jun;11(6):935-42
pubmed: 16772016
N Engl J Med. 2012 Apr 12;366(15):1423-32
pubmed: 22494122
Am J Epidemiol. 1984 Nov;120(5):653-69
pubmed: 6496446
PLoS Negl Trop Dis. 2013 Sep 26;7(9):e2412
pubmed: 24086778
Rev Infect Dis. 1989 May-Jun;11 Suppl 4:S830-9
pubmed: 2665015
Curr Top Microbiol Immunol. 2010;338:99-114
pubmed: 19802581
Nat Genet. 2005 May;37(5):507-13
pubmed: 15838506