PMID- 38181733
OWN - NLM
STAT- MEDLINE
DCOM- 20240108
LR  - 20240127
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 111
IP  - 1
DP  - 2024 Jan 4
TI  - Genetic determinants of IgG antibody response to COVID-19 vaccination.
PG  - 181-199
LID - S0002-9297(23)00437-8 [pii]
LID - 10.1016/j.ajhg.2023.12.005 [doi]
AB  - Human humoral immune responses to SARS-CoV-2 vaccines exhibit substantial 
      inter-individual variability and have been linked to vaccine efficacy. To 
      elucidate the underlying mechanism behind this variability, we conducted a 
      genome-wide association study (GWAS) on the anti-spike IgG serostatus of UK 
      Biobank participants who were previously uninfected by SARS-CoV-2 and had 
      received either the first dose (n = 54,066) or the second dose (n = 46,232) of 
      COVID-19 vaccines. Our analysis revealed significant genome-wide associations 
      between the IgG antibody serostatus following the initial vaccine and human 
      leukocyte antigen (HLA) class II alleles. Specifically, the HLA-DRB1( *)13:02 
      allele (MAF = 4.0%, OR = 0.75, p = 2.34e-16) demonstrated the most statistically 
      significant protective effect against IgG seronegativity. This protective effect 
      was driven by an alteration from arginine (Arg) to glutamic acid (Glu) at 
      position 71 on HLA-DRbeta1 (p = 1.88e-25), leading to a change in the electrostatic 
      potential of pocket 4 of the peptide binding groove. Notably, the impact of HLA 
      alleles on IgG responses was cell type specific, and we observed a shared genetic 
      predisposition between IgG status and susceptibility/severity of COVID-19. These 
      results were replicated within independent cohorts where IgG serostatus was 
      assayed by two different antibody serology tests. Our findings provide insights 
      into the biological mechanism underlying individual variation in responses to 
      COVID-19 vaccines and highlight the need to consider the influence of 
      constitutive genetics when designing vaccination strategies for optimizing 
      protection and control of infectious disease across diverse populations.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Bian, Shengzhe
AU  - Bian S
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China.
FAU - Guo, Xinxin
AU  - Guo X
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China.
FAU - Yang, Xilai
AU  - Yang X
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China.
FAU - Wei, Yuandan
AU  - Wei Y
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China.
FAU - Yang, Zijing
AU  - Yang Z
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China.
FAU - Cheng, Shiyao
AU  - Cheng S
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China.
FAU - Yan, Jiaqi
AU  - Yan J
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China.
FAU - Chen, Yongkun
AU  - Chen Y
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China.
FAU - Chen, Guo-Bo
AU  - Chen GB
AD  - Center for General Practice Medicine, Department of General Practice Medicine, 
      Clinical Research Institute, Zhejiang Provincial People's Hospital, People's 
      Hospital of Hangzhou Medical College, Hangzhou 310059, Zhejiang, P.R. China; Key 
      Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou 310063, 
      Zhejiang, P.R. China.
FAU - Du, Xiangjun
AU  - Du X
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China; Key Laboratory of Tropical Disease 
      Control, Ministry of Education, Sun Yat-sen University, Guangzhou 510006, P.R. 
      China.
FAU - Francis, Stephen S
AU  - Francis SS
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery, 
      University of California, San Francisco, San Francisco, CA 94143, USA; Helen 
      Diller Family Comprehensive Cancer Center, University of California, San 
      Francisco, San Francisco, CA 94143, USA; Weill Institute for Neurosciences, 
      University of California, San Francisco, San Francisco, CA 94158, USA.
FAU - Shu, Yuelong
AU  - Shu Y
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China; Institute of Pathogen Biology, Chinese 
      Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, P.R. 
      China. Electronic address: shuylong@mail.sysu.edu.cn.
FAU - Liu, Siyang
AU  - Liu S
AD  - School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 
      Shenzhen 518107, P.R. China; School of Public Health (Shenzhen), Sun Yat-sen 
      University, Guangzhou 510006, P.R. China. Electronic address: 
      liusy99@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Immunoglobulin G)
RN  - 0 (COVID-19 Vaccines)
SB  - IM
MH  - Humans
MH  - *Immunoglobulin G
MH  - Antibody Formation/genetics
MH  - COVID-19 Vaccines
MH  - Genome-Wide Association Study
MH  - *COVID-19/genetics/prevention & control
MH  - SARS-CoV-2
MH  - Vaccination
PMC - PMC10806743
OTO - NOTNLM
OT  - COVID-19
OT  - IgG response to vaccines
OT  - cross-ancestry
OT  - electrostatic potential energy
OT  - fine-mapping
OT  - genome-wide association study
OT  - human leukocyte antigen
OT  - transcriptome-wide association study
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2024/01/06 10:41
MHDA- 2024/01/08 06:42
PMCR- 2024/01/04
CRDT- 2024/01/05 18:26
PHST- 2023/08/04 00:00 [received]
PHST- 2023/12/01 00:00 [revised]
PHST- 2023/12/04 00:00 [accepted]
PHST- 2024/01/08 06:42 [medline]
PHST- 2024/01/06 10:41 [pubmed]
PHST- 2024/01/05 18:26 [entrez]
PHST- 2024/01/04 00:00 [pmc-release]
AID - S0002-9297(23)00437-8 [pii]
AID - 10.1016/j.ajhg.2023.12.005 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2024 Jan 4;111(1):181-199. doi: 10.1016/j.ajhg.2023.12.005.