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  Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia

Kumar, V., Cheng, S.-C., Johnson, M. D., Smeekens, S., Wojtowicz, A., Giamarellos-Bourboulis, E., et al. (2014). Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia. Nature Communications, 5: 5:4675. doi:10.1038/ncomms5675.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-A840-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-A841-9
Genre: Journal Article

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 Creators:
Kumar, Vinod, Author
Cheng, Shih-Chin, Author
Johnson, Melissa D., Author
Smeekens, Sanne, Author
Wojtowicz, Agnieszka, Author
Giamarellos-Bourboulis, Evangelos, Author
Karjalainen, Juha, Author
Franke, Lude, Author
Withoff, Sebo, Author
Plantinga, Theo S., Author
van de Veerdonk, Frank, Author
van der Meer, Jos, Author
Joosten, Leo A. B., Author
Sokol, Harry, Author
Bauer, Hermann1, Author              
Herrmann, Bernhard G.1, Author              
Bochud, Pierre-Yves, Author
Marchetti, Oscar, Author
Perfect, John R., Author
Xavier, Ramnik, Author
Kullberg, Bart Jan, AuthorWijmenga, Cisca, AuthorNetea, Mihai, Author more..
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              

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 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.

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 Dates: 2014-09-08
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/ncomms5675
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 5 Sequence Number: 5:4675 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723