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. 2022 Nov 14:13:1054147.
doi: 10.3389/fimmu.2022.1054147. eCollection 2022.

Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines

Ping Li  1 , Dawei Shi  2 , Wenlong Shen  1 , Shu Shi  1 , Xinjie Guo  1 , Jia Li  3 , Sihong Xu  2 , Yan Zhang  1 , Zhihu Zhao  1
Affiliations

Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines

Ping Li et al. Front Immunol. .

Abstract

Vaccines are a key weapon against the COVID-19 pandemic caused by SARS-CoV-2. However, there are inter-individual differences in immune response to SARS-CoV-2 vaccines and genetic contributions to these differences have barely been investigated. Here, we performed genome-wide association study (GWAS) of antibody levels in 168 inactivated SARS-CoV-2 vaccine recipients. A total of 177 SNPs, corresponding to 41 independent loci, were identified to be associated with IgG, total antibodies or neutral antibodies. Specifically, the rs4543780, the intronic variant of FAM89A gene, was associated with total antibodies level and was annotated as a potential regulatory variant affecting gene expression of FAM89A, a biomarker differentiating bacterial from viral infections in febrile children. These findings might advance our knowledge of the molecular mechanisms driving immunity to SARS-CoV-2 vaccine.

Keywords: COVID-19; GWAS; SARS-CoV-2; SNP; antibody; vaccine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Demographic characteristics and antibody levels of the 168 study subjects. (A) Vaccine type distribution; (B) Sex ratio; (C) Age distribution; (D) Distribution of days between the 2nd dose and blood draw; (E) Level of IgG, IgM, IgA, total antibodies (Ab) and neutralizing antibodies (NAbs) S/CO: sample/cutoff. (F) Percentage of positive individuals for IgG, IgM, IgA, Ab and NAbs.
Figure 2
Figure 2
Manhattan plot summaries of GWAS results for antibody response. (A) Results for IgG level; (B) Results for Ab level; (C) Results for NAbs level.
Figure 3
Figure 3
Annotation of the significant association SNP rs4543780. (A) LocusZoom plot showed the P value of the SNPs centering the lead SNP rs4543780, linkage disequilibrium degree, the recombination rate (top panel), SNP hits in GWAS catalogue (middle panel) and the genes in the region (bottom panel). 1:231038685_C/T indicated rs4543780 residing in chr1: 231038685 with reference allele of C and alternative allele of T; (B) DNase-seq peaks in the region of rs4543780 annotated by RegulomeDB. The yellow vertical line indicated the position of rs4543780.
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