Department of Economics and Business Economics

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Tarunveer S Ahluwalia, University of Copenhagen
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  • Anders U Eliasen, University of Copenhagen
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  • Astrid Sevelsted, University of Copenhagen
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  • Casper-Emil T Pedersen, University of Copenhagen
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  • Jakob Stokholm, University of Copenhagen
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  • Bo Chawes, University of Copenhagen
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  • Jette Bork-Jensen, University of Copenhagen
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  • Niels Grarup, University of Copenhagen
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  • Oluf Pedersen, University of Copenhagen
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  • Torben Hansen, University of Copenhagen
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  • Allan Linneberg, Center for Clinical Research and Disease Prevention, Frederiksberg Hospital, Denmark.
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  • Amitabh Sharma, Harvard School of Dental Medicine and Harvard Medical School
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  • Scott T Weiss, Harvard School of Dental Medicine and Harvard Medical School
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  • Michael D Evans, Univ Minnesota, University of Minnesota Twin Cities, University of Minnesota System, University of Minnesota Duluth, Dept Earth & Environm Sci
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  • Daniel J Jackson, Department of Psychiatry, University of Wisconsin-Madison, Wisconsin, USA; Department of Neurology, University of Wisconsin-Madison, Wisconsin, USA.
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  • Andreanne Morin, University of Chicago, Chicago, Illinois.
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  • Karen A Krogfelt, Bacteria, Parasites and Fungi Department, Statens Serum Institute, Copenhagen, Denmark.
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  • Susanne Schjørring, Bacteria, Parasites and Fungi Department, Statens Serum Institute, Copenhagen, Denmark.
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  • Preben B Mortensen
  • David M Hougaard, iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Lundbeck Fdn Initiat Integrat Psychiat Res
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  • Jonas Bybjerg-Grauholm, iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Lundbeck Fdn Initiat Integrat Psychiat Res
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  • Marie Bækvad-Hansen, iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Lundbeck Fdn Initiat Integrat Psychiat Res
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  • Ole Mors
  • Merete Nordentoft, iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Lundbeck Fdn Initiat Integrat Psychiat Res
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  • Anders D Børglum
  • Thomas Werge, iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Lundbeck Fdn Initiat Integrat Psychiat Res
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  • Esben Agerbo
  • James E Gern, Department of Psychiatry, University of Wisconsin-Madison, Wisconsin, USA; Department of Neurology, University of Wisconsin-Madison, Wisconsin, USA.
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  • Robert F Lemanske, Department of Psychiatry, University of Wisconsin-Madison, Wisconsin, USA; Department of Neurology, University of Wisconsin-Madison, Wisconsin, USA.
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  • Carole Ober, University of Chicago, Chicago, Illinois.
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  • Anders G Pedersen, Technical University of Denmark
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  • Hans Bisgaard, University of Copenhagen
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  • Klaus Bønnelykke, University of Copenhagen

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
Article number6398
JournalNature Communications
Volume11
Issue1
Number of pages12
ISSN2041-1723
DOIs
Publication statusPublished - Dec 2020

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