Immunochip SNP Array Identifies Novel Genetic Variants Conferring Susceptibility to Candidaemia

Nat Commun. 2014 Sep 8;5:4675. doi: 10.1038/ncomms5675.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD58 Antigens / genetics*
  • Candidemia / genetics*
  • Case-Control Studies
  • Cornified Envelope Proline-Rich Proteins / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • GTPase-Activating Proteins / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide

Substances

  • CD58 Antigens
  • Cornified Envelope Proline-Rich Proteins
  • GTPase-Activating Proteins
  • LCE4A protein, human
  • TAGAP protein, human