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=2×10
−6, OR=0.66), located within
c6orf10, a potential downstream effecter of TNF-alpha, and one indicated by rs13437088 (p=9×10
−6, OR=1.3), located 30 kb centromeric of
HLA-B and 16 kb telomeric of
MICA. When
HLA-Cw*0602, rs2073048, and rs13437088 were all included in a logistic regression model, each of them was significantly associated with disease (p=3×10
−47, 6×10
−8, and 3×10
−7, respectively). Both putative loci were also significantly associated in the Han Chinese samples after controlling for the imputed
HLA-Cw*0602. A detailed analysis of
HLA-B in both populations demonstrated that
HLA-B*57 was associated with an increased risk of psoriasis and
HLA-B*40 a decreased risk, independently of
HLA-Cw*0602 and the
C6orf10 locus, suggesting the potential pathogenic involvement of
HLA-B. These results demonstrate that there are at least two additional loci within the MHC conferring risk of psoriasis.
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