Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia

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, Frank L. van de Veerdonk, Jos W.M. van der Meer, Leo A.B. Joosten, Harry Sokol, Hermann Bauer, Bernhard G. Herrmann, Pierre-Yves Bochud, Oscar Marchetti, John R. Perfect, Ramnik J. Xavier, Bart Jan Kullberg, Cisca Wijmenga and Mihai G. Netea ()
Additional contact information
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
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
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
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
Ramnik J. Xavier: The Broad Institute of Massachusetts Institute of Technology and Harvard University
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

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5675

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