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Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia

Author

Listed:
  • Vinod Kumar

    (University of Groningen, University Medical Center Groningen, P.O. Box 30001)

  • Shih-Chin Cheng

    (Radboud University Medical Center, P.O. Box 9101)

  • Melissa D. Johnson

    (Duke University Medical Center, Duke Box 102359
    Campbell University School of Pharmacy, P.O. Box 1090)

  • Sanne P Smeekens

    (Radboud University Medical Center, P.O. Box 9101)

  • Agnieszka Wojtowicz

    (Service des Maladies Infectieuses, Centre Hospitalier Universitaire Vaudoises)

  • Evangelos Giamarellos-Bourboulis

    (University of Athens, Medical School
    Center for Sepsis Control and Care, Jena University Hospital)

  • Juha Karjalainen

    (University of Groningen, University Medical Center Groningen, P.O. Box 30001)

  • Lude Franke

    (University of Groningen, University Medical Center Groningen, P.O. Box 30001)

  • Sebo Withoff

    (University of Groningen, University Medical Center Groningen, P.O. Box 30001)

  • Theo S Plantinga

    (Radboud University Medical Center, P.O. Box 9101)

  • Frank L. van de Veerdonk

    (Radboud University Medical Center, P.O. Box 9101)

  • Jos W.M. van der Meer

    (Radboud University Medical Center, P.O. Box 9101)

  • Leo A.B. Joosten

    (Radboud University Medical Center, P.O. Box 9101)

  • Harry Sokol

    (The Broad Institute of Massachusetts Institute of Technology and Harvard University
    Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School)

  • Hermann Bauer

    (Max Planck Institute for Molecular Genetics)

  • Bernhard G. Herrmann

    (Max Planck Institute for Molecular Genetics)

  • Pierre-Yves Bochud

    (Service des Maladies Infectieuses, Centre Hospitalier Universitaire Vaudoises)

  • Oscar Marchetti

    (Service des Maladies Infectieuses, Centre Hospitalier Universitaire Vaudoises)

  • John R. Perfect

    (Duke University Medical Center, Duke Box 102359
    Campbell University School of Pharmacy, P.O. Box 1090)

  • Ramnik J. Xavier

    (The Broad Institute of Massachusetts Institute of Technology and Harvard University
    Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School)

  • Bart Jan Kullberg

    (Radboud University Medical Center, P.O. Box 9101)

  • Cisca Wijmenga

    (University of Groningen, University Medical Center Groningen, P.O. Box 30001)

  • Mihai G. Netea

    (Radboud University Medical Center, P.O. Box 9101)

Abstract

Candidaemia is the fourth most common cause of bloodstream infection, with a high mortality rate of up to 40%. Identification of host genetic factors that confer susceptibility to candidaemia may aid in designing adjunctive immunotherapeutic strategies. Here we hypothesize that variation in immune genes may predispose to candidaemia. We analyse 118,989 single-nucleotide polymorphisms (SNPs) across 186 loci known to be associated with immune-mediated diseases in the largest candidaemia cohort to date of 217 patients of European ancestry and a group of 11,920 controls. We validate the significant associations by comparison with a disease-matched control group. We observe significant association between candidaemia and SNPs in the CD58 (P=1.97 × 10−11; odds ratio (OR)=4.68), LCE4A-C1orf68 (P=1.98 × 10−10; OR=4.25) and TAGAP (P=1.84 × 10−8; OR=2.96) loci. Individuals carrying two or more risk alleles have an increased risk for candidaemia of 19.4-fold compared with individuals carrying no risk allele. We identify three novel genetic risk factors for candidaemia, which we subsequently validate for their role in antifungal host defence.

Suggested Citation

  • Vinod Kumar & Shih-Chin Cheng & Melissa D. Johnson & Sanne P Smeekens & Agnieszka Wojtowicz & Evangelos Giamarellos-Bourboulis & Juha Karjalainen & Lude Franke & Sebo Withoff & Theo S Plantinga & Fran, 2014. "Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5675
    DOI: 10.1038/ncomms5675
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