Carriers of Rare Missense Variants in IFIH1 Are Protected from Psoriasis

Testing of ∼25,000 putative functional single-nucleotide polymorphisms (SNPs) across the human genome in a genetic association study has identified three psoriasis genes, IL12B , IL23R , and IL13 . We now report evidence for the association of psoriasis risk with missense SNPs in the interferon induced with helicase C domain 1 gene ( IFIH1 ). The rare alleles of two independent SNPs were associated with decreased risk of psoriasis—rs35667974 (Ile923Val): odds ratio (OR) for minor allele carriers is 0.43, P =2.36 × 10 −5 (2,098 cases vs. 1,748 controls); and rs10930046 (His460Arg): OR for minor allele carriers is 0.51, P =6.47 × 10 −4 (2,098 cases vs. 1,744 controls). Compared to noncarriers, carriers of the 923Val and/or 460Arg variants were protected from psoriasis (OR=0.46, P =5.56 × 10 −8 ). To our knowledge, these results suggest that IFIH1 is a previously unreported psoriasis gene.