Genetic variation is a key factor influencing cytokine production capacity,but which genetic loci regulate cytokine production before and after vaccination,particularly in African population is unknown.Here,we aimed t...Genetic variation is a key factor influencing cytokine production capacity,but which genetic loci regulate cytokine production before and after vaccination,particularly in African population is unknown.Here,we aimed to identify single-nucleotide polymorphisms(SNPs)controlling cytokine responses after microbial stimulation in infants of West-African ancestry,comprising of low-birth-weight neonates randomized to bacillus Calmette-Gue rin(BCG)vaccine-at-birth or to the usual delayed BCG.Genome-wide cytokine cytokine quantitative trait loci(cQTL)mapping revealed 12 independent loci,of which the LINC01082-LINC00917 locus influenced more than half of the cytokine-stimulation pairs assessed.Furthermore,nine distinct cQTLs were found among infants randomized to BCG.Functional validation confirmed that several complement genes affect cytokine response after BCG vaccination.We observed a limited overlap of common cQTLs between the West-African infants and cohorts of Western European individuals.These data reveal strong population-specific genetic effects on cytokine production and may indicate new opportunities for therapeutic intervention and vaccine development in African populations.展开更多
基金supported by the Spinoza grant of the Netherlands Organization for Scientific Research and an ERC Advanced Grant(grant number833247)supported by the European Research Council(starting grant ERC-2009-StG-243149)+3 种基金the Novo Nordisk Foundation(research professorship grant to P.A.)the Danish National Research Foundation(grant DNRF108)the DANIDA,European Union FP7,and OPTIMUNISE(grant Health-F3-2011-261375 to the Bandim Health Project)supported by the Hypathia tenure track grant Radboud UMC。
文摘Genetic variation is a key factor influencing cytokine production capacity,but which genetic loci regulate cytokine production before and after vaccination,particularly in African population is unknown.Here,we aimed to identify single-nucleotide polymorphisms(SNPs)controlling cytokine responses after microbial stimulation in infants of West-African ancestry,comprising of low-birth-weight neonates randomized to bacillus Calmette-Gue rin(BCG)vaccine-at-birth or to the usual delayed BCG.Genome-wide cytokine cytokine quantitative trait loci(cQTL)mapping revealed 12 independent loci,of which the LINC01082-LINC00917 locus influenced more than half of the cytokine-stimulation pairs assessed.Furthermore,nine distinct cQTLs were found among infants randomized to BCG.Functional validation confirmed that several complement genes affect cytokine response after BCG vaccination.We observed a limited overlap of common cQTLs between the West-African infants and cohorts of Western European individuals.These data reveal strong population-specific genetic effects on cytokine production and may indicate new opportunities for therapeutic intervention and vaccine development in African populations.
