Fine mapping of the psoriasis susceptibility gene PSORS1: a reassessment of risk associated with a putative risk haplotype lacking HLA-Cw6

2.50
Hdl Handle:
http://hdl.handle.net/2336/2786
Title:
Fine mapping of the psoriasis susceptibility gene PSORS1: a reassessment of risk associated with a putative risk haplotype lacking HLA-Cw6
Authors:
Abecasis, G; Allen, M; Barker, J; Burden, D; Capon, F; Christophers, E; Elder, JT; Fischer, J; Gudjonsson, JE; Huffmeier, U; Jenisch, S; Karason, A; Kere, J; Nair, RP; Novelli, G; Prud´homme, JF; Qin, ZHS; Samuelsson, L; Sanchez, F; Saarialho-Kere, U; Stahle, M; Stuart, P; Tillman, D; Traupe, H; Trembath, R; Valdimarsson, H; Veal, C; Voorhees, JJ; Weichenthal, M
Citation:
J. Invest. Dermatol. 2005, 124(5):921-30
Issue Date:
May-2005
Abstract:
Human leukocyte antigen (HLA)-Cw6 has long been associated with psoriasis, and PSORS1 (psoriasis susceptibility 1), a major gene for psoriasis susceptibility, has been mapped to its vicinity. A previous analysis identified multiple risk haplotypes carrying HLA-Cw6 and one haplotype (cluster 17, HLA-Cw8-B65) that appeared to carry risk for psoriasis but did not carry HLA-Cw6. This haplotype was very similar to other risk haplotypes for at least 60 kb telomeric to HLA-C, suggesting identity by descent with the remaining risk chromosomes. The association, however, between psoriasis and this haplotype as assessed by the transmission/disequilibrium test (TDT) was of borderline significance (p-value 0.048). In order to better assess the risk associated with cluster 17, a multicenter collaboration typed additional subjects for a single marker (M6S161) for which one allele (249 bp) was found only on cluster 17. The new sample included 1275 pedigrees as well as 300 cases and 913 controls. Transmission of this allele to affected individuals was examined using the TDT and the pedigree disequilibrium test (PDT), and case-control samples were analyzed by a trend test across genotype categories. By all methods, the newly acquired genotypes failed to confirm the association originally reported, despite adequate power. In contrast, the 248 bp allele, which is found on all HLA-Cw6-positive risk haplotypes as well as several non-risk haplotypes, shows significant excess transmission for all cohorts. Taken together, these results indicate that cluster 17 does not carry a psoriasis-susceptibility allele, and expand the PSORS1 risk interval to approximately 300 kb.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.nature.com/jid/journal/v124/n5/full/5602799a.html

Full metadata record

DC FieldValue Language
dc.contributor.authorAbecasis, G-
dc.contributor.authorAllen, M-
dc.contributor.authorBarker, J-
dc.contributor.authorBurden, D-
dc.contributor.authorCapon, F-
dc.contributor.authorChristophers, E-
dc.contributor.authorElder, JT-
dc.contributor.authorFischer, J-
dc.contributor.authorGudjonsson, JE-
dc.contributor.authorHuffmeier, U-
dc.contributor.authorJenisch, S-
dc.contributor.authorKarason, A-
dc.contributor.authorKere, J-
dc.contributor.authorNair, RP-
dc.contributor.authorNovelli, G-
dc.contributor.authorPrud´homme, JF-
dc.contributor.authorQin, ZHS-
dc.contributor.authorSamuelsson, L-
dc.contributor.authorSanchez, F-
dc.contributor.authorSaarialho-Kere, U-
dc.contributor.authorStahle, M-
dc.contributor.authorStuart, P-
dc.contributor.authorTillman, D-
dc.contributor.authorTraupe, H-
dc.contributor.authorTrembath, R-
dc.contributor.authorValdimarsson, H-
dc.contributor.authorVeal, C-
dc.contributor.authorVoorhees, JJ-
dc.contributor.authorWeichenthal, M-
dc.date.accessioned2006-05-17T14:49:25Z-
dc.date.available2006-05-17T14:49:25Z-
dc.date.issued2005-05-
dc.identifier.citationJ. Invest. Dermatol. 2005, 124(5):921-30en
dc.identifier.issn0022-202X-
dc.identifier.pmid15854032-
dc.identifier.doi10.1111/j.0022-202X.2005.23729.x-
dc.identifier.urihttp://hdl.handle.net/2336/2786-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractHuman leukocyte antigen (HLA)-Cw6 has long been associated with psoriasis, and PSORS1 (psoriasis susceptibility 1), a major gene for psoriasis susceptibility, has been mapped to its vicinity. A previous analysis identified multiple risk haplotypes carrying HLA-Cw6 and one haplotype (cluster 17, HLA-Cw8-B65) that appeared to carry risk for psoriasis but did not carry HLA-Cw6. This haplotype was very similar to other risk haplotypes for at least 60 kb telomeric to HLA-C, suggesting identity by descent with the remaining risk chromosomes. The association, however, between psoriasis and this haplotype as assessed by the transmission/disequilibrium test (TDT) was of borderline significance (p-value 0.048). In order to better assess the risk associated with cluster 17, a multicenter collaboration typed additional subjects for a single marker (M6S161) for which one allele (249 bp) was found only on cluster 17. The new sample included 1275 pedigrees as well as 300 cases and 913 controls. Transmission of this allele to affected individuals was examined using the TDT and the pedigree disequilibrium test (PDT), and case-control samples were analyzed by a trend test across genotype categories. By all methods, the newly acquired genotypes failed to confirm the association originally reported, despite adequate power. In contrast, the 248 bp allele, which is found on all HLA-Cw6-positive risk haplotypes as well as several non-risk haplotypes, shows significant excess transmission for all cohorts. Taken together, these results indicate that cluster 17 does not carry a psoriasis-susceptibility allele, and expand the PSORS1 risk interval to approximately 300 kb.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://www.nature.com/jid/journal/v124/n5/full/5602799a.htmlen
dc.subjectCase-Control Studiesen
dc.subjectGene Frequencyen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectHLA-C Antigensen
dc.subjectHaplotypesen
dc.subjectHumansen
dc.subjectPsoriasisen
dc.subjectRisk Assessmenten
dc.titleFine mapping of the psoriasis susceptibility gene PSORS1: a reassessment of risk associated with a putative risk haplotype lacking HLA-Cw6en
dc.typeArticleen
dc.format.digYES-

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