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.
Li
Yonghong
Y
Celera, Alameda, California 94502, USA. yonghong.li@celera.com
Liao
Wilson
W
Cargill
Michele
M
Chang
Monica
M
Matsunami
Nori
N
Feng
Bing-Jian
BJ
Poon
Annie
A
Callis-Duffin
Kristina P
KP
Catanese
Joseph J
JJ
Bowcock
Anne M
AM
Leppert
Mark F
MF
Kwok
Pui-Yan
PY
Krueger
Gerald G
GG
Begovich
Ann B
AB
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
C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1