Journal
NATURE GENETICS
Volume 42, Issue 11, Pages 985-U106Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.694
Keywords
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Categories
Funding
- Wellcome Trust [083948/Z/07/Z]
- Netherlands Organization for Health Research and Development (P.L.J.M.Z.)
- Swedish Medical Research Council
- Karolinska Institutet
- Karolinska University Hospital
- Psoriasis Foundation
- AFA Insurance and Welander Finsen Foundation
- Association for the Defence of Psoriasis Patients
- Psoriasis Association and the Cecil King Memorial Foundation
- Swedish Psoriasis Association
- German Research Foundation [Tr 228/5-4, Re 679/104]
- Interdisciplinary Centre for Clinical Research of the University of Erlangen-Nuremberg [IZKF B32/A8]
- Spanish Ministry of Science and Innovation [SAF 2008-00357]
- Departments of Health and Universities and Innovation
- Genetic Repository in Ireland for Psoriasis and Psoriatic Arthritis
- Irish Health Research Board
- Wellcome Trust and Science Foundation Ireland [078173/Z/05/Z, 068545/Z/02]
- National Institute for Health Research
- Manchester Biomedical Research Centre
- Arthritis Research UK [17552]
- Wolfson-Royal Society
- Generation Trust
- UK Medical Research Council [G0601387]
- Department of Health through the National Institute for Health Research (NIHR)
- St. Thomas' National Health Service (NHS) Foundation Trust
- King's College London
- Medical Research Council [G0000934]
- Wellcome Trust [083948/Z/07/Z, 078173/Z/05/Z] Funding Source: Wellcome Trust
- MRC [G0901310, G19/2, G0000934, G0600705, G0700314, G0601387, G0800582] Funding Source: UKRI
- Medical Research Council [G0901310, G0800582, G0600705, G19/2, G9817803B, G0700314, G0601387, G0600698B, G0000934] Funding Source: researchfish
- National Institute for Health Research [CL-2008-06-002, NF-SI-0507-10379, PDA/02/06/016] Funding Source: researchfish
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To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 x 10(-8) and two loci with a combined P < 5 x 10(-7)). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 x 10(-6)). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis.
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