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

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  • Tarunveer S. Ahluwalia

    (University of Copenhagen
    Steno Diabetes Center Copenhagen
    University of Copenhagen)

  • Anders U. Eliasen

    (University of Copenhagen
    Technical University of Denmark)

  • Astrid Sevelsted

    (University of Copenhagen)

  • Casper-Emil T. Pedersen

    (University of Copenhagen)

  • Jakob Stokholm

    (University of Copenhagen)

  • Bo Chawes

    (University of Copenhagen)

  • Jette Bork-Jensen

    (University of Copenhagen)

  • Niels Grarup

    (University of Copenhagen)

  • Oluf Pedersen

    (University of Copenhagen)

  • Torben Hansen

    (University of Copenhagen)

  • Allan Linneberg

    (The Capital Region
    University of Copenhagen)

  • Amitabh Sharma

    (Harvard Medical School)

  • Scott T. Weiss

    (Harvard Medical School)

  • Michael D. Evans

    (University of Minnesota)

  • Daniel J. Jackson

    (University of Wisconsin)

  • Andreanne Morin

    (University of Chicago)

  • Karen A. Krogfelt

    (Parasites and Fungi, Statens Serum Institut
    Roskilde University)

  • Susanne Schjørring

    (Parasites and Fungi, Statens Serum Institut)

  • Preben B. Mortensen

    (The Lundbeck Foundation Initiative for Integrated Psychiatric Research
    Aarhus University
    CIRRAU—Center for Integrated Register-Based Research at Aarhus University)

  • David M. Hougaard

    (The Lundbeck Foundation Initiative for Integrated Psychiatric Research
    Statens Serum Institut
    SSI)

  • Jonas Bybjerg-Grauholm

    (The Lundbeck Foundation Initiative for Integrated Psychiatric Research
    Statens Serum Institut
    SSI)

  • Marie Bækvad-Hansen

    (The Lundbeck Foundation Initiative for Integrated Psychiatric Research
    Statens Serum Institut
    SSI)

  • Ole Mors

    (The Lundbeck Foundation Initiative for Integrated Psychiatric Research
    Aarhus University Hospital—Psychiatry)

  • Merete Nordentoft

    (The Lundbeck Foundation Initiative for Integrated Psychiatric Research
    Copenhagen University Hospital)

  • Anders D. Børglum

    (The Lundbeck Foundation Initiative for Integrated Psychiatric Research
    Aarhus University
    Central Region Denmark)

  • Thomas Werge

    (The Lundbeck Foundation Initiative for Integrated Psychiatric Research
    Copenhagen University Hospital
    Copenhagen Mental Health Services
    University of Copenhagen)

  • Esben Agerbo

    (The Lundbeck Foundation Initiative for Integrated Psychiatric Research
    Aarhus University
    CIRRAU—Center for Integrated Register-Based Research at Aarhus University)

  • James E. Gern

    (University of Wisconsin)

  • Robert F. Lemanske

    (University of Wisconsin)

  • Carole Ober

    (University of Chicago)

  • Anders G. Pedersen

    (Technical University of Denmark)

  • Hans Bisgaard

    (University of Copenhagen)

  • Klaus Bønnelykke

    (University of Copenhagen)

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.

Suggested Citation

  • 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 Linneber, 2020. "FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19814-6
    DOI: 10.1038/s41467-020-19814-6
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