Genome-Wide Association Study Identifies Genetic Loci for Antibody Response to SARS-CoV-2 Vaccines in Patients With Systemic Autoimmune Diseases and Healthy Individuals.

Abstract

The efficacy of nucleic acid-based vaccines against SARS-CoV-2 varies across individuals, partly due to genetic factors influencing neutralizing antibody production. In patients with systemic autoimmune diseases (SADs), this response may be further altered by immune dysregulation. We conducted a genome-wide association study (GWAS) to identify genetic variants associated with postvaccination anti-SARS-CoV-2 IgG antibody levels and to assess whether these associations differ between patients with SAD and healthy individuals. The study included 165 participants (138 with SADs, 27 healthy controls), all of whom received nucleic acid-based vaccines. Antibody levels targeting the spike protein receptor-binding domain (RBD) and nucleocapsid were measured between 1 and 12 months after vaccination. GWAS results were metaanalyzed with data from a previously published GWAS with 1076 healthy individuals. We identified a novel association near <i>RACGAP1</i> (rs706785; β_meta = -0.30, <i>P</i> _meta = 3.85 × 10^-8) and replicated a known association at HLA-DRB1 position 71 (β_meta = -0.23, <i>P</i> _meta = 1.94 × 10^-11). No significant interactions were observed between genotype and disease status. This study highlights both MHC and non-MHC genetic contributions to SARS-CoV-2 vaccine responses and suggests these effects are consistent across patients with SADs and healthy individuals, supporting standard vaccination strategies for individuals with systemic autoimmune conditions.