Genome-wide association analysis identifies three psoriasis susceptibility loci.
We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10⁻¹¹), one at FBXL19 (rs10782001, combined P = 9 × 10⁻¹⁰) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10⁻⁸). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10⁻⁵; rs10782001, combined P = 4 × 10⁻⁸; and rs12586317, combined P = 6 × 1⁻⁵) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10⁻⁸; rs10782001, combined P = 2 × 10⁻⁶; and rs12586317, combined P = 1 × 10⁻⁶). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10⁻⁷).
Stuart
Philip E
PE
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Nair
Rajan P
RP
Ellinghaus
Eva
E
Ding
Jun
J
Tejasvi
Trilokraj
T
Gudjonsson
Johann E
JE
Li
Yun
Y
Weidinger
Stephan
S
Eberlein
Bernadette
B
Gieger
Christian
C
Wichmann
H Erich
HE
Kunz
Manfred
M
Ike
Robert
R
Krueger
Gerald G
GG
Bowcock
Anne M
AM
Mrowietz
Ulrich
U
Lim
Henry W
HW
Voorhees
John J
JJ
Abecasis
Gonçalo R
GR
Weichenthal
Michael
M
Franke
Andre
A
Rahman
Proton
P
Gladman
Dafna D
DD
Elder
James T
JT
D015535:Arthritis, Psoriatic / Q000235:genetics; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D044783:F-Box Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D008824:Michigan; D000072000:NF-KappaB Inhibitor alpha; D009523:Newfoundland and Labrador; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D009864:Ontario; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D011565:Psoriasis / Q000235:genetics*
D004268:DNA-Binding Proteins; D044783:F-Box Proteins; C499971:FBXL19 protein, human; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C465641:PSMA6 protein, human; D046988:Proteasome Endopeptidase Complex