Causal associations between antibody-mediated immune responses to infectious agents and cardiovascular inflammatory...

A two-sample Mendelian randomization study was performed to evaluate causal associations between 46 pathogen-specific antibodies and six cardiovascular inflammatory diseases: myocarditis, pericarditis, endocarditis, coronary atherosclerosis (CAS), polyarteritis nodosa (PAN), and giant cell arteritis (GCA). Antibody data came from UK Biobank, diseases data came from FinnGen. Instrumental variables were selected using strict (p < 5 × 10^-8) and lenient threshold (p < 5 × 10^-6). Benjamini-Hochberg method was used to control FDR; FDR‑adjusted q < 0.05 defined "robust associations." Under strict threshold, robust associations were observed for HHV-7 U14 antibody levels with myocarditis (OR = 2.049, 95% CI: 1.325-3.168, p = .001, FDR = 0.044), EBV EBNA-1 antibody levels with CAS (OR = 0.909, 95% CI: 0.866-0.954, p = 1.00E-04, FDR = 0.001), and EBV EA-D antibody levels with GCA (OR = 0.410, 95% CI: 0.247-0.680, p = .001, FDR = 0.007). Under lenient threshold, EBV EBNA-1 antibody levels (OR = 0.924, 95% CI: 0.889-0.960, p = 5.03E-05, FDR = 0.012) and anti-Helicobacter pylori IgG seropositivity (OR = 1.050, 95% CI: 1.021-1.080, p = .001, FDR = 0.047) were robustly associated with CAS. No significant horizontal pleiotropy or heterogeneity was detected, and reverse MR did not support reverse causation. This study provides genetic evidence for causal associations between pathogen‑specific antibodies with myocarditis, CAS and GCA. Associations identified under strict threshold represent more robust evidence, whereas those under lenient threshold are hypothesis-generating. Validation in more rigorous designs and non-European populations is warranted.