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Genetic regulators of cytokine responses in children from West Africa: the impact of BCG vaccination

Article scientifique 2022 Anglais

Résumé

Abstract 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 (cQTLs) after microbial stimulation in infants of West-African ancestry, comprising of low-birth-weight neonates randomized to BCG vaccine-at-birth (intervention) or to the usual delayed BCG (control). Genome-wide cytokine QTL-mapping revealed 12 independent cQTLs, 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 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.

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Boahen, C., Moorlag, S., Jensen, K., Matzaraki, V., Fanucchi, S., Monteiro, I., Bree, C., Fok, E., Mhlanga, M., Joosten, L., Aaby, P., Benn, C., Netea, M., Kumar, V. (2022). Genetic regulators of cytokine responses in children from West Africa: the impact of BCG vaccination. https://doi.org/10.21203/rs.3.rs-1502935/v1

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Auteur(s)

Collins Kwadwo Boahen Simmone J. C. F. Moorlag Kristoffer Jarlov Jensen Vasiliki Matzaraki Stephanie Fanucchi Ivan Monteiro Charlotte de Bree Ezio T. Fok Musa M. Mhlanga Leo A. B. Joosten Peter Aaby Christine Stabell Benn Mihai G. Netea Vinod Kumar

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