A genome-wide association study of host genetic determinants of the antibody response to Anthrax Vaccine Adsorbed.
Several lines of evidence have supported a host genetic contribution to vaccine response, but genome-wide assessments for specific determinants have been sparse. Here we describe a genome-wide association study (GWAS) of protective antigen-specific antibody (AbPA) responses among 726 European-Americans who received Anthrax Vaccine Adsorbed (AVA) as part of a clinical trial. After quality control, 736,996 SNPs were tested for association with the AbPA response to 3 or 4 AVA vaccinations given over a 6-month period. No SNP achieved the threshold of genome-wide significance (p=5 × 10(-8)), but suggestive associations (p<1 × 10(-5)) were observed for SNPs in or near the class II region of the major histocompatibility complex (MHC), in the promoter region of SPSB1, and adjacent to MEX3C. Multivariable regression modeling suggested that much of the association signal within the MHC corresponded to previously identified HLA DR-DQ haplotypes involving component HLA-DRB1 alleles of *15:01, *01:01, or *01:02. We estimated the proportion of additive genetic variance explained by common SNP variation for the AbPA response after the 6 month vaccination. This analysis indicated a significant, albeit imprecisely estimated, contribution of variation tagged by common polymorphisms (p=0.032). Future studies will be required to replicate these findings in European Americans and to further elucidate the host genetic factors underlying variable immune response to AVA.
Department of Biostatistical Sciences, Wake Forest University Health Sciences, Winston Salem, NC 27157-1063, USA. npajewsk@wakehealth.edu
Nicholas M
NM
Pajewski
Sadeep
S
Shrestha
Conrad P
CP
Quinn
Scott D
SD
Parker
Howard
H
Wiener
Brahim
B
Aissani
Brett A
BA
McKinney
Gregory A
GA
Poland
Jeffrey C
JC
Edberg
Robert P
RP
Kimberly
Jianming
J
Tang
Richard A
RA
Kaslow
D000328:Adult; D022122:Anthrax Vaccines / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation / Q000235:genetics*; D005260:Female; D005802:Genes, MHC Class II; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D044465:White People / Q000235:genetics
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; C515359:MEX3C protein, human; D016601:RNA-Binding Proteins; D050826:Suppressor of Cytokine Signaling Proteins