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Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus.
- Source :
-
PLoS genetics [PLoS Genet] 2011 Oct; Vol. 7 (10), pp. e1002341. Date of Electronic Publication: 2011 Oct 27. - Publication Year :
- 2011
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Abstract
- Systemic lupus erythematosus (SLE) is a complex trait characterised by the production of a range of auto-antibodies and a diverse set of clinical phenotypes. Currently, ~8% of the genetic contribution to SLE in Europeans is known, following publication of several moderate-sized genome-wide (GW) association studies, which identified loci with a strong effect (OR>1.3). In order to identify additional genes contributing to SLE susceptibility, we conducted a replication study in a UK dataset (870 cases, 5,551 controls) of 23 variants that showed moderate-risk for lupus in previous studies. Association analysis in the UK dataset and subsequent meta-analysis with the published data identified five SLE susceptibility genes reaching genome-wide levels of significance (P(comb)<5×10(-8)): NCF2 (P(comb) = 2.87×10(-11)), IKZF1 (P(comb) = 2.33×10(-9)), IRF8 (P(comb) = 1.24×10(-8)), IFIH1 (P(comb) = 1.63×10(-8)), and TYK2 (P(comb) = 3.88×10(-8)). Each of the five new loci identified here can be mapped into interferon signalling pathways, which are known to play a key role in the pathogenesis of SLE. These results increase the number of established susceptibility genes for lupus to ~30 and validate the importance of using large datasets to confirm associations of loci which moderately increase the risk for disease.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Case-Control Studies
Cohort Studies
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Interferon-Induced Helicase, IFIH1
Interferons genetics
Polymorphism, Single Nucleotide
Signal Transduction
DEAD-box RNA Helicases genetics
Ikaros Transcription Factor genetics
Interferon Regulatory Factors genetics
Interferons metabolism
Lupus Erythematosus, Systemic genetics
NADPH Oxidases genetics
TYK2 Kinase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 7
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 22046141
- Full Text :
- https://doi.org/10.1371/journal.pgen.1002341