FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses
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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 language | English |
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Article number | 6398 |
Journal | Nature Communications |
Volume | 11 |
Number of pages | 12 |
ISSN | 2041-1723 |
DOIs | |
Publication status | Published - 2020 |
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