Recent genome-wide association studies (GWAS) have identified multiple genetic risk factors for psoriasis, but data on their association with age of onset have been marginally explored. The goal of this study was to evaluate known risk alleles of psoriasis for association with age of psoriasis onset in three well-defined case-only cohorts totaling 1,498 psoriasis patients. We selected 39 genetic variants from psoriasis GWAS and tested these variants for association with age of psoriasis onset in a meta-analysis. We found that rs10484554 and rs12191877 near HLA-C and rs17716942 near IFIH1 were associated with age of psoriasis onset with false discovery rate < 0.05. The association between rs17716942 and age of onset was not replicated in a fourth independent cohort of 489 patients ( ). The imputed HLA-C*06:02 allele demonstrated a much stronger association with age of psoriasis onset than rs10484554 and rs12191877. We conclude that despite the discovery of numerous psoriasis risk alleles, HLA-C*06:02 still plays the most important role in determining the age of onset of psoriasis. Larger studies are needed to evaluate the contribution of other risk alleles, including IFIH1, to age of psoriasis onset. 1. Introduction Psoriasis is an inflammatory, immune-mediated disorder of the skin, joints, and nails with an estimated prevalence of 2-3% of the population. Henseler and Christophers divided psoriasis into two subtypes. Type I psoriasis manifests before age 40 with peak onset at 16–22 years, and Type II psoriasis begins after age 40 with peak onset at 57–60 years [1]. Type I and II psoriasis have been shown to differ clinically in their severity, relapse frequency, and family history [1, 2]. The clinical differences in Type I and Type II psoriasis are paralleled by genetic differences. Type I psoriasis has a stronger genetic basis as a greater proportion of patients had a family history of psoriasis, and has stronger HLA-C*06 associations; however, Type II psoriasis is negative in family history, and is not associated with HLA-C*06 [1, 3, 4]. Over the past few years, over 36 novel psoriasis loci have been identified through genome-wide association studies (GWAS) [5–13]. However, it is not known to what degree these susceptibility alleles influence the age of onset of psoriasis. Here, we examined 39 of these genetic variants in 3 cohorts of psoriasis cases to ascertain whether any of these loci were preferentially associated with the age of psoriasis onset. 2. Materials and Methods The SNPs were selected from psoriasis GWAS conducted in Caucasian populations
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