FUT2-ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses

Tarunveer S Ahluwalia, Anders U Eliasen, Astrid Sevelsted, Casper-Emil T Pedersen, Jakob Stokholm, Bo Chawes, Jette Bork-Jensen, Niels Grarup, Oluf Pedersen, Torben Hansen, Allan Linneberg, Amitabh Sharma, Scott T Weiss, Michael D Evans, Daniel J Jackson, Andreanne Morin, Karen A Krogfelt, Susanne Schjørring, Preben B Mortensen, David M HougaardJonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Ole Mors, Merete Nordentoft, Anders D Børglum, Thomas Werge, Esben Agerbo, James E Gern, Robert F Lemanske, Carole Ober, Anders G Pedersen, Hans Bisgaard, Klaus Bønnelykke

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)6398
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 16 2020

Keywords

  • ABO Blood-Group System/genetics
  • Asthma/genetics
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Epistasis, Genetic
  • Female
  • Fucosyltransferases/genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Male
  • Pneumococcal Infections/genetics
  • Polymorphism, Single Nucleotide
  • Streptococcus pneumoniae/pathogenicity

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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