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

免疫学 生命银行 免疫系统 生物 炎症 抗体 等位基因 过敏 疾病 免疫失调 遗传学 医学 基因 内科学
作者
Amanda Y. Chong,Nicole Brenner,Andrés Jimenez-Kaufmann,Adrián Cortés,Michael Hill,Thomas J. Littlejohns,James J. Gilchrist,Benjamin P. Fairfax,Julian C. Knight,Flavia Hodel,Jacques Fellay,Gil McVean,Andrés Moreno‐Estrada,Tim Waterboer,Adrian V. S. Hill,Alexander J. Mentzer
出处
期刊:American Journal of Human Genetics [Elsevier]
卷期号:111 (2): 295-308 被引量:2
标识
DOI:10.1016/j.ajhg.2023.12.013
摘要

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 genome-wide 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.

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