Journal Article

Genome-wide association analysis identifies three psoriasis susceptibility loci

Tejasvi, Trilokraj, Ike, Robert, Voorhees, John J, Li, Yun, Ding, Jun, Gladman, Dafna D, Nair, Rajan P, Mrowietz, Ulrich, Franke, Andre, Bowcock, Anne M, Rahman, Proton, Weichenthal, Michael, Ellinghaus, Eva, Stuart, Philip E, Krueger, Gerald G, Gudjonsson, Johann E, Elder, James T, Eberlein, Bernadette, Weidinger, Stephan, Gieger, Christian, Lim, Henry W, Wichmann, H Erich, Kunz, Manfred, Abecasis, Gonçalo R

2010

Overview

James Elder and colleagues report meta-analyses of two psoriasis genome-wide association studies with replication in additional cohorts. They make use of imputation using both the HapMap and initial 1000 Genomes Project datasets and identify three new psoriasis susceptibility loci. We carried out a meta-analysis of two recent psoriasis genome-wide association studies 1 , 2 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 × 10 −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 3 association signal near RNF114 (rs495337, combined P = 2 × 10 −7 ).

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/205/2138 / 631/208/727/2000 / 692/699/249/1313/1758 / Agriculture / Animal Genetics and Genomics / Arthritis, Psoriatic - genetics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Care and treatment / Case-Control Studies / Dermatology / Disease susceptibility / DNA-Binding Proteins - genetics / F-Box Proteins - genetics / Fundamental and applied biological sciences. Psychology / Gene Function / Genetic aspects / Genetic Predisposition to Disease / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study / Genotype / Genotype & phenotype / Germany / Haplotypes / Human Genetics / Humans / I-kappa B Proteins - genetics / Inflammatory bowel disease / letter / Medical research / Medical sciences / Meta-analysis / Michigan / Newfoundland and Labrador / NF-KappaB Inhibitor alpha / Nitric oxide / Nitric Oxide Synthase Type II - genetics / Ontario / Polymerase chain reaction / Polymorphism, Single Nucleotide / Proteasome Endopeptidase Complex - genetics / Psoriasis / Psoriasis - genetics / Psoriasis. Parapsoriasis. Lichen / Quality control / Single nucleotide polymorphisms / Skin diseases