title: Carriers of rare missense variants in IFIH1 are protected from psoriasis.
abstract: 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.
authors.affiliation: Celera, Alameda, California 94502, USA. yonghong.li@celera.com
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Li
authors.forename: Wilson
authors.initials: W
authors.lastname: Liao
authors.forename: Michele
authors.initials: M
authors.lastname: Cargill
authors.forename: Monica
authors.initials: M
authors.lastname: Chang
authors.forename: Nori
authors.initials: N
authors.lastname: Matsunami
authors.forename: Bing-Jian
authors.initials: BJ
authors.lastname: Feng
authors.forename: Annie
authors.initials: A
authors.lastname: Poon
authors.forename: Kristina P
authors.initials: KP
authors.lastname: Callis-Duffin
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Catanese
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
authors.forename: Mark F
authors.initials: MF
authors.lastname: Leppert
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Krueger
authors.forename: Ann B
authors.initials: AB
authors.lastname: Begovich
mesh_terms: D000328:Adult; D015551:Autoimmunity / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors
chemical_list: C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1