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The Capital Region of Denmark - a part of Copenhagen University Hospital
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FUT2-ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses

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Asthma with severe exacerbation is the most common cause of hospitalization among young children. We aim to increase the understanding of this clinically important disease entity through a genome-wide association study. The discovery analysis comprises 2866 children experiencing severe asthma exacerbation between ages 2 and 6 years, and 65,415 non-asthmatic controls, and we replicate findings in 918 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) birth cohorts. We identify rs281379 near FUT2/MAMSTR on chromosome 19 as a novel risk locus (OR = 1.18 (95% CI = 1.11-1.25), Pdiscovery = 2.6 × 10-9) as well as a biologically plausible interaction between functional variants in FUT2 and ABO. We further discover and replicate a potential causal mechanism behind this interaction related to S. pneumoniae respiratory illnesses. These results suggest a novel mechanism of early childhood asthma and demonstrates the importance of phenotype-specificity for discovery of asthma genes and epistasis.

Original languageEnglish
Article number6398
JournalNature Communications
Volume11
Issue number1
Pages (from-to)6398
ISSN2041-1723
DOIs
Publication statusPublished - 16 Dec 2020

ID: 61546213