Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases Agents: A Genome-Wide and HLA Association Study.
LASSO
genome-wide association study
human leukocyte antigen
infections
serology
Journal
Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
11
08
2020
accepted:
22
09
2020
entrez:
18
11
2020
pubmed:
19
11
2020
medline:
19
11
2020
Statut:
epublish
Résumé
Infectious diseases are causally related to a large array of noncommunicable diseases (NCDs). Identifying genetic determinants of infections and antibody-mediated immune responses may shed light on this relationship and provide therapeutic targets for drug and vaccine development. We used the UK biobank cohort of up to 10 000 serological measurements of infectious diseases and genome-wide genotyping. We used data on 13 pathogens to define 46 phenotypes: 15 seropositivity case-control phenotypes and 31 quantitative antibody measurement phenotypes. For each of these, we performed genome-wide association studies (GWAS) using the fastGWA linear mixed model package and human leukocyte antigen (HLA) classical allele and amino acid residue associations analyses using Lasso regression for variable selection. We included a total of 8735 individuals for case-control phenotypes, and an average (range) of 4286 (276-8555) samples per quantitative analysis. Fourteen of the GWAS yielded a genome-wide significant ( We have identified multiple genetic variants associated with antibody immune response to 13 infections, many of which are biologically plausible therapeutic or vaccine targets. This may help prioritize future research and drug development.
Sections du résumé
BACKGROUND
BACKGROUND
Infectious diseases are causally related to a large array of noncommunicable diseases (NCDs). Identifying genetic determinants of infections and antibody-mediated immune responses may shed light on this relationship and provide therapeutic targets for drug and vaccine development.
METHODS
METHODS
We used the UK biobank cohort of up to 10 000 serological measurements of infectious diseases and genome-wide genotyping. We used data on 13 pathogens to define 46 phenotypes: 15 seropositivity case-control phenotypes and 31 quantitative antibody measurement phenotypes. For each of these, we performed genome-wide association studies (GWAS) using the fastGWA linear mixed model package and human leukocyte antigen (HLA) classical allele and amino acid residue associations analyses using Lasso regression for variable selection.
RESULTS
RESULTS
We included a total of 8735 individuals for case-control phenotypes, and an average (range) of 4286 (276-8555) samples per quantitative analysis. Fourteen of the GWAS yielded a genome-wide significant (
CONCLUSIONS
CONCLUSIONS
We have identified multiple genetic variants associated with antibody immune response to 13 infections, many of which are biologically plausible therapeutic or vaccine targets. This may help prioritize future research and drug development.
Identifiants
pubmed: 33204752
doi: 10.1093/ofid/ofaa450
pii: ofaa450
pmc: PMC7641500
doi:
Types de publication
Journal Article
Langues
eng
Pagination
ofaa450Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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