Multiple Loci within the Major Histocompatibility Complex Confer Risk of Psoriasis |
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| Authors: | Bing-Jian Feng, Liang-Dan Sun, Razieh Soltani-Arabshahi, Anne M. Bowcock, Rajan P. Nair, Philip Stuart, James T. Elder, Steven J. Schrodi, Ann B. Begovich, Gon alo R. Abecasis, Xue-Jun Zhang, Kristina P. Callis-Duffin, Gerald G. Krueger, David E. Goldgar |
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| Affiliation: | Bing-Jian Feng, Liang-Dan Sun, Razieh Soltani-Arabshahi, Anne M. Bowcock, Rajan P. Nair, Philip Stuart, James T. Elder, Steven J. Schrodi, Ann B. Begovich, Gonçalo R. Abecasis, Xue-Jun Zhang, Kristina P. Callis-Duffin, Gerald G. Krueger, and David E. Goldgar |
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| Abstract: | Psoriasis is a common inflammatory skin disease characterized by thickened scaly red plaques. Previously we have performed a genome-wide association study (GWAS) on psoriasis with 1,359 cases and 1,400 controls, which were genotyped for 447,249 SNPs. The most significant finding was for SNP rs12191877, which is in tight linkage disequilibrium with HLA-Cw*0602, the consensus risk allele for psoriasis. However, it is not known whether there are other psoriasis loci within the MHC in addition to HLA-C. In the present study, we searched for additional susceptibility loci within the human leukocyte antigen (HLA) region through in-depth analyses of the GWAS data; then, we followed up our findings in an independent Han Chinese 1,139 psoriasis cases and 1,132 controls. Using the phased CEPH dataset as a reference, we imputed the HLA-Cw*0602 in all samples with high accuracy. The association of the imputed HLA-Cw*0602 dosage with disease was much stronger than that of the most significantly associated SNP, rs12191877. Adjusting for HLA-Cw*0602, there were two remaining association signals: one demonstrated by rs2073048 (p | |
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