GWAS identifies genetic loci for antibody response to SARS-CoV-2 vaccines in patients with systemic autoimmune diseases and healthy individuals

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 post-vaccination anti-SARS-CoV-2 IgG antibody levels and to assess whether these associations differ between SAD patients 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 one and twelve months after vaccination. GWAS results were meta-analyzed with data from a previously published GWAS of 1,076 healthy individuals. We identified a novel association near RACGAP1 (rs706785; βmeta=–0.30, Pmeta=3.85×10−□) and replicated a known association at HLA-DRB1 position 71 (βmeta=–0.23, Pmeta=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 SAD patients and healthy individuals, supporting standard vaccination strategies for individuals with systemic autoimmune conditions.