A multi-tiered, case-control association study using a collection of over 25,000 gene-centric SNPs, identified association between a 3’UTR SNP in IL12B, rs3212227, and psoriasis risk (allelic Pcomb = 7.85 x 10-10) in three independent sample sets (Cargill et al. 2007) confirming the results of a previous small candidate gene study in Japanese (Tsunemi et al. 2002). To determine whether any other SNPs in this gene region were associated with psoriasis we used a combination of tag SNPs (N=27), which had the highest average power to detect disease-associated variants under a conservative disease model, and functional SNPs (N=3) to genotype our three sample sets and identified a second risk allele, rs6887695 (allelic Pcomb = 4.08 x 10-8), located approximately 60 kb upstream of the IL12B coding region that exhibited association with psoriasis after adjustment for rs3212227 (Cargill et al. 2007). Together these two SNPs marked a common IL12B risk haplotype (ORcommon 1.40, Pcomb = 8.11 x 10-9) and a less frequent protective haplotype (ORcommon 0.58, Pcomb = 5.65 x 10-12), which were statistically significant in all three studies. However, this set of 30 SNPs did not allow us to explore whether the psoriasis association observed with rs3212227 and rs6887695 was due to LD with other variants not interrogated. Consequently, we selected 20 additional SNPs for genotyping in the three psoriasis case-control sample sets and report the data for all 51 IL12B-region SNPs here.
Available at: http://works.bepress.com/steve_schrodi/23/