PMID- 33204752
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231104
IS  - 2328-8957 (Print)
IS  - 2328-8957 (Electronic)
IS  - 2328-8957 (Linking)
VI  - 7
IP  - 11
DP  - 2020 Nov
TI  - Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases 
      Agents: A Genome-Wide and HLA Association Study.
PG  - ofaa450
LID - 10.1093/ofid/ofaa450 [doi]
LID - ofaa450
AB  - 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: 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: 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 (P < 5 x10(-8)) locus at the major histocompatibility 
      complex (MHC) on chromosome 6. Outside the MHC, we found a total of 60 loci, 
      multiple associated with Epstein-Barr virus (EBV)-related NCDs (eg, RASA3, 
      MED12L, and IRF4). FUT2 was also identified as an important gene for 
      polyomaviridae. HLA analysis highlighted the importance of DRB1*09:01, 
      DQB1*02:01, DQA1*01:02, and DQA1*03:01 in EBV serologies and of DRB1*15:01 in 
      polyomaviridae. 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.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of 
      Infectious Diseases Society of America.
FAU - Butler-Laporte, Guillaume
AU  - Butler-Laporte G
AUID- ORCID: 0000-0001-5388-0396
AD  - Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, 
      Quebec, Canada.
AD  - Department of Epidemiology, Biostatistics and Occupational Health, McGill 
      University, Montreal, Quebec, Canada.
FAU - Kreuzer, Devin
AU  - Kreuzer D
AD  - Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, 
      Quebec, Canada.
FAU - Nakanishi, Tomoko
AU  - Nakanishi T
AD  - Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, 
      Quebec, Canada.
AD  - Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
AD  - Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate 
      School of Medicine, Kyoto University, Kyoto, Japan.
FAU - Harroud, Adil
AU  - Harroud A
AD  - Department of Neurology, University of California San Francisco, San Francisco, 
      California, USA.
AD  - Weill Institute for Neurosciences, University of California San Francisco, San 
      Francisco, California, USA.
FAU - Forgetta, Vincenzo
AU  - Forgetta V
AUID- ORCID: 0000-0002-6061-4720
AD  - Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, 
      Quebec, Canada.
FAU - Richards, J Brent
AU  - Richards JB
AD  - Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, 
      Quebec, Canada.
AD  - Department of Epidemiology, Biostatistics and Occupational Health, McGill 
      University, Montreal, Quebec, Canada.
AD  - Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
AD  - Department of Twin Research, King's College London, London, UK.
LA  - eng
GR  - MC_PC_17228/MRC_/Medical Research Council/United Kingdom
GR  - MC_QA137853/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20200924
PL  - United States
TA  - Open Forum Infect Dis
JT  - Open forum infectious diseases
JID - 101637045
PMC - PMC7641500
OTO - NOTNLM
OT  - LASSO
OT  - genome-wide association study
OT  - human leukocyte antigen
OT  - infections
OT  - serology
EDAT- 2020/11/19 06:00
MHDA- 2020/11/19 06:01
PMCR- 2020/09/24
CRDT- 2020/11/18 06:00
PHST- 2020/08/11 00:00 [received]
PHST- 2020/09/22 00:00 [accepted]
PHST- 2020/11/18 06:00 [entrez]
PHST- 2020/11/19 06:00 [pubmed]
PHST- 2020/11/19 06:01 [medline]
PHST- 2020/09/24 00:00 [pmc-release]
AID - ofaa450 [pii]
AID - 10.1093/ofid/ofaa450 [doi]
PST - epublish
SO  - Open Forum Infect Dis. 2020 Sep 24;7(11):ofaa450. doi: 10.1093/ofid/ofaa450. 
      eCollection 2020 Nov.