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^*

^*Corresponding author voor dit werk

Onderzoeksoutput: Article › Academic › peer review

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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 bacillus Calmette–Guérin (BCG) vaccine-at-birth (intervention) or to the usual delayed BCG (control). Genome-wide cytokine QTL mapping revealed 12 independent cQTLs 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.

Originele taal-2	English
Pagina's (van-tot)	434-446
Aantal pagina's	13
Tijdschrift	Journal of Genetics and Genomics
Volume	50
Nummer van het tijdschrift	6
DOI's	https://doi.org/10.1016/j.jgg.2023.01.002
Status	Published - jun.-2023

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10.1016/j.jgg.2023.01.002Licentie: CC BY

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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, 50(6), 434-446. https://doi.org/10.1016/j.jgg.2023.01.002

@article{d57bc6e1564540d2948f07236ed5b502,

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 (cQTLs) 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 (intervention) or to the usual delayed BCG (control). Genome-wide cytokine QTL mapping revealed 12 independent cQTLs 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.",

keywords = "BCG, Cytokines, Genetic variation, Immunogenomics, QTL, West Africa",

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",

note = "Funding Information: 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 . Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = jun,

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

language = "English",

volume = "50",

pages = "434--446",

journal = "Journal of Genetics and Genomics",

issn = "1673-8527",

publisher = "Elsevier",

number = "6",

}

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, vol. 50, nr. 6, blz. 434-446. https://doi.org/10.1016/j.jgg.2023.01.002

TY - JOUR

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

N1 - Funding Information: 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 . Publisher Copyright: © 2023 The Authors

PY - 2023/6

Y1 - 2023/6

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

KW - Cytokines

KW - Genetic variation

KW - Immunogenomics

KW - QTL

KW - West Africa

U2 - 10.1016/j.jgg.2023.01.002

DO - 10.1016/j.jgg.2023.01.002

M3 - Article

C2 - 36681271

AN - SCOPUS:85149870152

SN - 1673-8527

VL - 50

SP - 434

EP - 446

JO - Journal of Genetics and Genomics

JF - Journal of Genetics and Genomics

IS - 6

ER -

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

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