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Ahluwalia, Tarunveer S; Eliasen, Anders U; Sevelsted, Astrid; Pedersen, Casper-Emil T; Stokholm, Jakob; Chawes, Bo; Bork-Jensen, Jette; Grarup, Niels; Pedersen, Oluf; Hansen, Torben; Linneberg, Allan; Sharma, Amitabh; Weiss, Scott T; Evans, Michael D; Jackson, Daniel J; Morin, Andreanne; Krogfelt, Karen A; Schjørring, Susanne; Mortensen, Preben B; Hougaard, David M; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Mors, Ole; Nordentoft, Merete; Børglum, Anders D; Werge, Thomas; Agerbo, Esben; Gern, James E; Lemanske, Jr, Robert F; Ober, Carole; Pedersen, Anders G; Bisgaard, Hans; Bønnelykke, Klaus
Nature communications, 12/2020, Volume: 11, Issue: 1Journal Article
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), P = 2.6 × 10 ) 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.
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