Genome-wide genetic associations with IFNγ response to smallpox vaccine

Race and sex-based differences in cytokine immune responses to smallpox vaccine in healthy individuals

“…The four major race/ethnicity groups based on the genomic data were: Caucasian (n=580); African-American (n=217); Hispanic (n=217); and other (n=57), including Asian, American Indian, Alaskan Native, Native Hawaiian, other Pacific Islander and subjects with unknown race/ethnicity. As previously reported, we observed a strong concordance between self-declared and genetic race/ethnicity for study participants with clear self-declaration [23,24]. The cell mediated immunity (CMI) variables for the study population (cytokine responses in response to vaccinia virus stimulation) have been previously described in detail and were characterized by a Th1-biased cytokine immune response pattern and a strong innate/proinflammatory cytokine response [21,22].…”

“…The statistical methods described herein are similar or identical to those published for our previous studies [20–24]. Study participants were asked to indicate their race and ethnicity via a questionnaire.…”

“…We also used the genetic data to categorize subjects (having chosen: “More than one race,” “Other,” or “Don’t Know”) into racial/ethnic groups. Our approach for racial/ethnic classification based on genetic data has been reported in detail elsewhere [20,23,24]. Briefly, we identified a collection of SNPs (n=22,863 SNPs) not in linkage disequilibrium with one another and applied a principal components approach to quantify population genetic similarity among the study subjects [25].…”

“…Subjects not clustering unambiguously into one of these three groups were retained as another genetic group labeled “Other.” The sex of the study participants was identified based on self-declaration and verified with genetic data, using the PLINK genome-wide association study (GWAS) to compute the inbreeding coefficients on the X chromosome. This assessment identified one individual as an XXY male (Klinefelter’s syndrome), who was excluded from the study [24]. Summaries of the measured immune response outcomes were obtained from per-subject medians of the replicates measured by the assays.…”

Cytokine Production Associated with Smallpox Vaccine Responses

“…Although no significant associations existed between SNP and total PBMC IFN-γ ELISpot results among the Caucasian subjects of the studied population, several significant associations were identified among the African–American subjects, including two SNPs (in NFIB and GNAI1 genes) correlated with a decrease in total IFN-γ ELISpot responses, and four SNPs (in FAS and OPRMI genes) correlated with an increase in total IFN-γ ELISpot responses. Additionally, one SNP near the DAOA gene was correlated with a decrease in serum IFN-γ levels, as measured by IFN-γ ELISAs) in both Caucasian and African–American populations [51]. …”