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  4. A common NFKB1 variant detected through antibody analysis in UK Biobank predicts risk of infection and allergy
 
research article

A common NFKB1 variant detected through antibody analysis in UK Biobank predicts risk of infection and allergy

Chong, Amanda Y.
•
Brenner, Nicole
•
Jimenez-Kaufmann, Andres
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February 1, 2024
American Journal Of Human Genetics

Infectious agents contribute significantly to the global burden of diseases through both acute infection and their chronic sequelae. We leveraged the UK Biobank to identify genetic loci that influence humoral immune response to multiple infections. From 45 genomewide association studies in 9,611 participants from UK Biobank, we identified NFKB1 as a locus associated with quantitative antibody responses to multiple pathogens, including those from the herpes, retro-, and polyoma-virus families. An insertion -deletion variant thought to affect NFKB1 expression (rs28362491), was mapped as the likely causal variant and could play a key role in regulation of the immune response. Using 121 infection- and inflammation -related traits in 487,297 UK Biobank participants, we show that the deletion allele was associated with an increased risk of infection from diverse pathogens but had a protective effect against allergic disease. We propose that altered expression of NFKB1, as a result of the deletion, modulates hematopoietic pathways and likely impacts cell survival, antibody production, and inflammation. Taken together, we show that disruptions to the tightly regulated immune processes may tip the balance between exacerbated immune responses and allergy, or increased risk of infection and impaired resolution of inflammation.

  • Details
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Type
research article
DOI
10.1016/j.ajhg.2023.12.013
Web of Science ID

WOS:001174779800001

Author(s)
Chong, Amanda Y.
Brenner, Nicole
Jimenez-Kaufmann, Andres
Cortes, Adrian
Hill, Michael
Littlejohns, Thomas J.
Gilchrist, James J.
Fairfax, Benjamin P.
Knight, Julian C.
Hodel, Flavia Aurelia  
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Date Issued

2024-02-01

Published in
American Journal Of Human Genetics
Volume

111

Issue

2

Subjects

Life Sciences & Biomedicine

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Genome-Wide Association

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Nf-Kappa-B

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Nfkb1 Promoter Polymorphism

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Susceptibility

•

Identification

•

Selection

•

Diseases

•

Reveals

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPFELLAY  
FunderGrant Number

Wellcome Trust Fellowship

SGL024\1096

National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)

Academy of Medical Sciences Starter Grant

MR/N028937/1

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Available on Infoscience
April 3, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/206834
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