title: Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.
abstract: Psoriasis is a common immune-mediated disorder that affects the skin, nails and joints. To identify psoriasis susceptibility loci, we genotyped 438,670 SNPs in 1,409 psoriasis cases and 1,436 controls of European ancestry. We followed up 21 promising SNPs in 5,048 psoriasis cases and 5,041 controls. Our results provide strong support for the association of at least seven genetic loci and psoriasis (each with combined P < 5 x 10(-8)). Loci with confirmed association include HLA-C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes that act downstream of TNF-alpha and regulate NF-kappaB signaling (TNIP1, TNFAIP3) and two genes involved in the modulation of Th2 immune responses (IL4, IL13). Although the proteins encoded in these loci are known to interact biologically, we found no evidence for epistasis between associated SNPs. Our results expand the catalog of genetic loci implicated in psoriasis susceptibility and suggest priority targets for study in other auto-immune disorders.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Rajan P
authors.initials: RP
authors.lastname: Nair
authors.forename: Kristina Callis
authors.initials: KC
authors.lastname: Duffin
authors.forename: Cynthia
authors.initials: C
authors.lastname: Helms
authors.forename: Jun
authors.initials: J
authors.lastname: Ding
authors.forename: Philip E
authors.initials: PE
authors.lastname: Stuart
authors.forename: David
authors.initials: D
authors.lastname: Goldgar
authors.forename: Johann E
authors.initials: JE
authors.lastname: Gudjonsson
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Trilokraj
authors.initials: T
authors.lastname: Tejasvi
authors.forename: Bing-Jian
authors.initials: BJ
authors.lastname: Feng
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruether
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Michael
authors.initials: M
authors.lastname: Weichenthal
authors.forename: Dafna
authors.initials: D
authors.lastname: Gladman
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schrodi
authors.forename: Sampath
authors.initials: S
authors.lastname: Prahalad
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Guthery
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
authors.forename: Wilson
authors.initials: W
authors.lastname: Liao
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Alan
authors.initials: A
authors.lastname: Menter
authors.forename: G Mark
authors.initials: GM
authors.lastname: Lathrop
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wise
authors.forename: Ann B
authors.initials: AB
authors.lastname: Begovich
authors.forename: John J
authors.initials: JJ
authors.lastname: Voorhees
authors.forename: James T
authors.initials: JT
authors.lastname: Elder
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Krueger
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics; D053759:Interleukin-23 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D015236:HLA-C Antigens; C500879:IL12B protein, human; C508598:IL4 protein, human; D053762:Interleukin-12 Subunit p40; D018793:Interleukin-13; D053759:Interleukin-23; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C117046:TNIP1 protein, human; D015847:Interleukin-4; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3