A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1

Strange, A., Capon, F., Spencer, C. C. A., Knight, J., Weale, M. E., Allen, M. H., Barton, A., Band, G., Bellenguez, C., Bergboer, J. G. M., BlackweL, J. M., Bramon, E., Bumpstead, S. J., Casas, J. P., Cork, M. J., Corvin, A., Deloukas, P., Dilthey, A., Duncanson, A., Edkins, S., EstiviL, X., Fitzgerald, O., FrEman, C., Giardina, E., Gray, E., Hofer, A., Hüffmeier, U., Hunt, S. E., Irvine, A. D., Jankowski, J., Kirby, B., Langford, C., Lascorz, J., Leman, J., Leslie, S., MaLbris, L., Markus, H. S., Mathew, C. G., McLean, W. H. I., McManus, R., MöSner, R., Moutsianas, L., Naluai, A. T., Nestle, F. O., NoveLi, G., Onoufriadis, A., Palmer, C. N. A., Perricone, C., Pirinen, M., Plomin, R., PoTer, S. C., Pujol, R. M., Rautanen, A., Riveira-Munoz, E., Ryan, A. W., Salmhofer, W., SamuelSon, L., Sawcer, S. J., Schalkwijk, J., Smith, C. H., Ståhle, M., Su, Z., Tazi-Ahnini, R., Traupe, H., Viswanathan, A. C., Warren, R. B., Weger, W., Wolk, K., Wod, N., Worthington, J., Young, H. S., Zeeuwen, P. L. J. M., Hayday, A., Burden, A. D., Griffiths, C. E. M., Kere, J., Reis, A., McVean, G., Evans, D. M., Brown, Matthew A., Barker, J. N., Peltonen, L., Donely, P., & Trembath, R. C. (2010) A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1. Nature Genetics, 42(11), pp. 985-990.

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To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P < 5-10 -8 and two loci with a combined P < 5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis.

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ID Code: 89382
Item Type: Journal Article
Refereed: Yes
Keywords: HLA C antigen, aminopeptidase, ERAP1 protein, human, article, controlled study, ERAP1 gene, gene interaction, gene locus, genetic association, genetic susceptibility, human, ifih1 gene, IL28RA gene, major clinical study, nfkbia gene, priority journal, psoriasis, REL gene, single nucleotide polymorphism, TRAF3IP2 gene, tyk2 gene, chromosome map, Europe, genetic predisposition, genetic variability, genetics, human chromosome, major histocompatibility complex, reference value, risk assessment, X chromosome, Aminopeptidases, Chromosome Mapping, Chromosomes, Human, Chromosomes, Human, X, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, HLA-C Antigens, Humans, Polymorphism, Single Nucleotide, Reference Values
DOI: 10.1038/ng.694
ISSN: 1061-4036
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 Nature America, Inc.
Deposited On: 21 Oct 2015 23:21
Last Modified: 22 Aug 2016 00:25

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