Genetic Causality of Antibody Immune Responses in Hemorrhagic Stroke

摘要

Hemorrhagic stroke,the second leading cause of stroke,is a severe medical emergency that often leads to severe disability or death;however,the causal relationship between antibody-mediated immune responses and hemorrhagic stroke remains unknown.This study aimed to investigate the potential causal relationship between antibody-mediated immune responses to infectious agents and hemorrhagic stroke using the two-sample Mendelian randomization (MR) method.Comprehensive analyses were conducted using publicly available data from genome-wide association study (GWAS),which involved the whole genomes of 9 724 European participants and 46 antibody measurement phenotypes,and summary statistics from the FinnGen dataset R12 (including intracerebral hemorrhage and subarachnoid hemorrhage) were used.The causal relationship between the aforementioned immune responses and hemorrhagic stroke was analyzed using inverse-variance weighting,MR–Egger regression,weighted median,weighted mode,simple mode,and MR–pleiotropy residual sum and outlier (MR–PRESSO),while various sensitivity analyses were performed to assess heterogeneity and pleiotropy in the study findings.Results showed that human herpes virus 7 (HHV–7) U14 antibody levels (OR:0.877,95% CI:0.797–0.964,P=0.007) exerted a protective effect against hemorrhagic stroke,and Chlamydia trachomatis (CT) tarp–D F2 antibody levels (OR:0.937,95% CI:0.885–0.992,P=0.025) had a potential protective effect;additionally,Epstein-Barr virus (EBV) ZEBRA antibody levels (OR:1.062,95% CI:1.012–1.114,P=0.014),human herpesvirus 6 (HHV–6) p101k antibody levels (OR:1.054,95% CI:1.002–1.108,P=0.042),and cytomegalovirus (CMV) pp150 antibody levels (OR:1.086,95% CI:1.002–1.176,P=0.045) were potential risk factors for the disease.No significant pleiotropy or heterogeneity was observed in any of the MR analyses.Collectively,these findings confirmed a significant causal relationship between antibody-mediated immune responses and hemorrhagic stroke,and this study contributed to a deeper understanding of the potential mechanisms underlying hemorrhagic stroke onset.

关键词

antibody immune response / hemorrhagic stroke / Mendelian randomization / causal inference