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

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

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6 Citations (Scopus)

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.

Original language	English
Journal	Journal of genetics and genomics = Yi chuan xue bao
Volume	50
Issue number	6
Pages (from-to)	434-446
Number of pages	13
ISSN	1673-8527
DOIs	https://doi.org/10.1016/j.jgg.2023.01.002
Publication status	Published - Jun 2023

Keywords

Infant, Newborn
Infant
Humans
Child
BCG Vaccine/genetics
Cytokines/genetics
Africa, Western
Vaccination

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10.1016/j.jgg.2023.01.002

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Boahen, C. K., Moorlag, S. J. C. F. M., Jensen, K. J., Matzaraki, V., Fanucchi, S., Monteiro, I., de Bree, C., Fok, E. T., Mhlanga, M., Joosten, L. A. B., Aaby, P., Benn, C. S., Netea, M. G., & Kumar, V. (2023). Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa. Journal of genetics and genomics = Yi chuan xue bao, 50(6), 434-446. https://doi.org/10.1016/j.jgg.2023.01.002

Boahen, CK, Moorlag, SJCFM, Jensen, KJ, Matzaraki, V, Fanucchi, S, Monteiro, I, de Bree, C, Fok, ET, Mhlanga, M, Joosten, LAB, Aaby, P, Benn, CS, Netea, MG & Kumar, V 2023, 'Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa', Journal of genetics and genomics = Yi chuan xue bao, vol. 50, no. 6, pp. 434-446. https://doi.org/10.1016/j.jgg.2023.01.002

@article{fd168850820f400d92663c27e131507a,

title = "Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa",

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-Gu{\'e}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.",

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

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doi = "10.1016/j.jgg.2023.01.002",

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T1 - Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa

AU - Boahen, Collins K

AU - Moorlag, S J C F M

AU - Jensen, Kristoffer Jarlov

AU - Matzaraki, Vasiliki

AU - Fanucchi, Stephanie

AU - Monteiro, Ivan

AU - de Bree, Charlotte

AU - Fok, Ezio T

AU - Mhlanga, Musa

AU - Joosten, Leo A B

AU - Aaby, Peter

AU - Benn, Christine Stabell

AU - Netea, Mihai G

AU - Kumar, Vinod

PY - 2023/6

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N2 - 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.

AB - 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.

KW - Infant, Newborn

KW - Infant

KW - Humans

KW - Child

KW - BCG Vaccine/genetics

KW - Cytokines/genetics

KW - Africa, Western

KW - Vaccination

UR - https://www.scopus.com/pages/publications/85149870152

U2 - 10.1016/j.jgg.2023.01.002

DO - 10.1016/j.jgg.2023.01.002

M3 - Journal article

C2 - 36681271

SN - 1673-8527

VL - 50

SP - 434

EP - 446

JO - Journal of genetics and genomics = Yi chuan xue bao

JF - Journal of genetics and genomics = Yi chuan xue bao

IS - 6

ER -

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

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