Elevated risk of invasive group a streptococcal disease and host genetic variation in the human leukocyte antigen locus

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Title: Elevated risk of invasive group a streptococcal disease and host genetic variation in the human leukocyte antigen locus
Authors: Parks, T
Elliot, K
Lamagni, T
Auckland, K
Mentzer, AJ
Guy, R
Cartledge, D
Strakova, L
O'Connor, D
Pollard, AJ
Neville, MJ
Mahajan, A
Ashrafian, H
Chapman, SJ
Hill, AVS
Sriskandan, S
Knight, JC
Item Type: Journal Article
Abstract: Invasive group A streptococcal (GAS) disease is uncommon but carries a high casefatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop lifethreatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1,540 controls. Using HLA imputation and linear mixed-models, we find each copy of the HLA-DQA1*01:03 allele associates with a two-fold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P=0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.
Issue Date: 29-Aug-2019
Date of Acceptance: 11-Jun-2019
URI: http://hdl.handle.net/10044/1/71595
ISSN: 1466-4879
Publisher: Springer Nature
Journal / Book Title: Genes and Immunity
Sponsor/Funder: National Institute for Health Research
National Institute for Health Research
GlaxoSmithKline Services Unlimited
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: HPRU-2012-10047
HPRU-2012-10047
PN1028 GS
RDA02 79560
Keywords: Immunology
1107 Immunology
Publication Status: Accepted
Embargo Date: 2020-02-29
Appears in Collections:Department of Medicine



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