Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa

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

doi:10.1016/j.jgg.2023.01.002

Volume 50 Issue 6

Jun. 2023

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Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa

doi: 10.1016/j.jgg.2023.01.002

a. Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands;
b. Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands;
c. Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Odense, DK-5000, Denmark;
d. Center for Clinical Research and Prevention, Frederiksberg and Bispebjerg Hospital, DK-2000, Frederiksberg, Denmark;
e. Lemba Therapeutics, Nijmegen, 6525 GA, the Netherlands;
f. Bandim Health Project, Indepth Network, Bissau, codex 1004, Guinea-Bissau;
g. Epigenomics & Single Cell Biophysics Group, Department of Cell Biology FNWI, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, 6525 HP, the Netherlands;
h. Department of Human Genetics, Radboud University Medical Center, 6525 HP, the Netherlands;
i. Bandim Health Project, Statens Serum Institut, Copenhagen S, DK-2300, Denmark;
j. Danish Institute for Advanced Study, University of Southern Denmark, Odense, DK-5000, Denmark;
k. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands;
l. Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Germany;
m. University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, 9700 RB, the Netherlands;
n. Nitte (Deemed to be University), Nitte University Centre for Science Education and Research (NUCSER), Medical Sciences Complex, Deralakatte, Mangalore, 575018, India

Funds:

The authors thank all volunteers from the BHP cohort and 500FG and 300BCG cohorts for participation in the studies. This work was supported by the Spinoza grant of the Netherlands Organization for Scientific Research and an ERC Advanced Grant (grant number 833247). The original trial was supported by the European Research Council (starting grant ERC-2009-StG-243149), 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). V. K was supported by the Hypathia tenure track grant Radboud UMC.

Received Date: 2022-11-13
Accepted Date: 2023-01-03
Rev Recd Date: 2022-12-21
Publish Date: 2023-01-18

Abstract

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 after microbial stimulation in infants of West-African ancestry, comprising of low-birth-weight neonates randomized to bacillus Calmette–Guérin (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.
- Cytokines,
- Genetic variation,
- West Africa,
- Immunogenomics,
- QTL,
- BCG

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References(56)

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