| Literature DB >> 33328473 |
Tarunveer S Ahluwalia1,2,3, Anders U Eliasen1,4, Astrid Sevelsted1, Casper-Emil T Pedersen1, Jakob Stokholm1, Bo Chawes1, Jette Bork-Jensen5, Niels Grarup5, Oluf Pedersen5, Torben Hansen5, Allan Linneberg6,7, Amitabh Sharma8, Scott T Weiss8, Michael D Evans9, Daniel J Jackson10, Andreanne Morin11, Karen A Krogfelt12,13, Susanne Schjørring12, Preben B Mortensen14,15,16, David M Hougaard14,17,18, Jonas Bybjerg-Grauholm14,17,18, Marie Bækvad-Hansen14,17,18, Ole Mors14,19, Merete Nordentoft14,20, Anders D Børglum14,21,22, Thomas Werge14,20,23,24, Esben Agerbo14,15,16, James E Gern10, Robert F Lemanske10, Carole Ober11, Anders G Pedersen4, Hans Bisgaard1, Klaus Bønnelykke25.
Abstract
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.Entities:
Year: 2020 PMID： 33328473 DOI： 10.1038/s41467-020-19814-6
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919