A Genome-wide Association Study of Host Genetic Determinants of the Antibody Response to Anthrax Vaccine Adsorbed

摘要: Several lines of evidence have supported a host genetic contribution to vaccine response, but genome-wide assessments for specific determinants been sparse. Here we describe association study (GWAS) protective antigen-specific antibody (AbPA) responses among 726 European-Americans who received Anthrax Vaccine Adsorbed (AVA) as part clinical trial. After quality control, 736,996 SNPs were tested with the AbPA response 3 or 4 AVA vaccinations given over 6-month period. No SNP achieved threshold significance (p=5 × 10(-8)), suggestive associations (p<1 10(-5)) observed in near class II region major histocompatibility complex (MHC), promoter SPSB1, and adjacent MEX3C. Multivariable regression modeling suggested that much signal within MHC corresponded previously identified HLA DR-DQ haplotypes involving component HLA-DRB1 alleles *15:01, *01:01, *01:02. We estimated proportion additive variance explained by common variation after 6 month vaccination. This analysis indicated significant, albeit imprecisely estimated, tagged polymorphisms (p=0.032). Future studies will be required replicate these findings European Americans further elucidate factors underlying variable immune AVA.