title: Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci.
abstract: Psoriasis (PS) and Crohn disease (CD) have been shown to be epidemiologically, pathologically, and therapeutically connected, but little is known about their shared genetic causes. We performed meta-analyses of five published genome-wide association studies on PS (2,529 cases and 4,955 controls) and CD (2,142 cases and 5,505 controls), followed up 20 loci that showed strongest evidence for shared disease association and, furthermore, tested cross-disease associations for previously reported PS and CD risk alleles in additional 6,115 PS cases, 4,073 CD cases, and 10,100 controls. We identified seven susceptibility loci outside the human leukocyte antigen region (9p24 near JAK2, 10q22 at ZMIZ1, 11q13 near PRDX5, 16p13 near SOCS1, 17q21 at STAT3, 19p13 near FUT2, and 22q11 at YDJC) shared between PS and CD with genome-wide significance (p < 5 × 10(-8)) and confirmed four already established PS and CD risk loci (IL23R, IL12B, REL, and TYK2). Three of the shared loci are also genome-wide significantly associated with PS alone (10q22 at ZMIZ1, p(rs1250544) = 3.53 × 10(-8), 11q13 near PRDX5, p(rs694739) = 3.71 × 10(-09), 22q11 at YDJC, p(rs181359) = 8.02 × 10(-10)). In addition, we identified one susceptibility locus for CD (16p13 near SOCS1, p(rs4780355) = 4.99 × 10(-8)). Refinement of association signals identified shared genome-wide significant associations for exonic SNPs at 10q22 (ZMIZ1) and in silico expression quantitative trait locus analyses revealed that the associations at ZMIZ1 and near SOCS1 have a potential functional effect on gene expression. Our results show the usefulness of joint analyses of clinically distinct immune-mediated diseases and enlarge the map of shared genetic risk loci.
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Ellinghaus
authors.forename: Eva
authors.initials: E
authors.lastname: Ellinghaus
authors.forename: Rajan P
authors.initials: RP
authors.lastname: Nair
authors.forename: Philip E
authors.initials: PE
authors.lastname: Stuart
authors.forename: Tõnu
authors.initials: T
authors.lastname: Esko
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.forename: Sophie
authors.initials: S
authors.lastname: Debrus
authors.forename: John V
authors.initials: JV
authors.lastname: Raelson
authors.forename: Trilokraj
authors.initials: T
authors.lastname: Tejasvi
authors.forename: Majid
authors.initials: M
authors.lastname: Belouchi
authors.forename: Sarah L
authors.initials: SL
authors.lastname: West
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Barker
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
authors.forename: Külli
authors.initials: K
authors.lastname: Kingo
authors.forename: Tobias
authors.initials: T
authors.lastname: Balschun
authors.forename: Orazio
authors.initials: O
authors.lastname: Palmieri
authors.forename: Vito
authors.initials: V
authors.lastname: Annese
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: H Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mathew
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.forename: Susanna
authors.initials: S
authors.lastname: Nikolaus
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: James T
authors.initials: JT
authors.lastname: Elder
authors.forename: Michael
authors.initials: M
authors.lastname: Weichenthal
authors.forename: Michael
authors.initials: M
authors.lastname: Nothnagel
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
mesh_terms: D003424:Crohn Disease / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011565:Psoriasis / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics