Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia.

Nat Commun
Authors
Keywords
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.

Year of Publication
2014
Journal
Nat Commun
Volume
5
Pages
4675
Date Published
2014 Sep 08
ISSN
2041-1723
URL
DOI
10.1038/ncomms5675
PubMed ID
25197941
PubMed Central ID
PMC5142444
Links
Grant list
310372 / European Research Council / International
K23 AI051537 / AI / NIAID NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
K23AI51537 / AI / NIAID NIH HHS / United States