Genome-wide association analysis identifies three psoriasis susceptibility loci.

Authors:
Philip E Stuart, Rajan P Nair, Eva Ellinghaus, Jun Ding, Trilokraj Tejasvi, Johann E Gudjonsson, Yun Li, Stephan Weidinger, Bernadette Eberlein, Christian Gieger, H Erich Wichmann, Manfred Kunz, Robert Ike, Gerald G Krueger, Anne M Bowcock, Ulrich Mrowietz, Henry W Lim, John J Voorhees, Gonçalo R Abecasis, Michael Weichenthal, Andre Franke, Proton Rahman, Dafna D Gladman, James T Elder
Year of publication:
2010
Volume:
42
Issue:
11
Issn:
1061-4036
Journal title abbreviated:
NAT GENET
Journal title long:
Nature genetics
Impact factor:
31.616
Abstract:
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).