1. ¹Celera, Alameda, California, USA
2. ²Department of Dermatology, University of California, San Francisco, California, USA
3. ³Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA
4. ⁴Department of Dermatology, University of Utah, Salt Lake City, Utah, USA
5. ⁵LineaGen Research Corporation, Salt Lake City, Utah, USA
6. ⁶Division of Human Genetics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA
7. ⁷Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
8. ⁸Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

Correspondence: Dr Yonghong Li, Discovery Research, Celera, 1401 Harbor Bay Parkway, Alameda, California 94502, USA. E-mail: yonghong.li@celera.com

⁹Current address: Roche Molecular Diagnostics, Pleasanton, CA, USA

Received 12 June 2008; Revised 25 July 2008; Accepted 13 August 2008; Published online 16 October 2008.

Abstract

Predisposition to psoriasis is known to be affected by genetic variation in HLA-C, IL12B, and IL23R, and although other psoriasis-associated variants have been identified, incontrovertible statistical evidence for these markers has not yet been obtained. To help resolve this issue, we tested 15 single-nucleotide polymorphisms (SNPs) from 7 putative psoriasis-risk genes in 1,448 psoriasis patients and 1,385 control subjects; 3 SNPs, rs597980 in ADAM33, rs6908425 in CDKAL1 and rs3789604 in PTPN22, were significant with the same risk allele as in prior reports (one-sided P<0.05, false discovery rate<0.15). These three markers were tested in a fourth sample set (599 cases and 299 controls); one marker, rs597980, replicated (one-sided P<0.05) and the other two had odds ratios with the same directionality as in the original sample sets. Mantel–Haenszel meta-analyses of all available case–control data, including those published by other groups, showed that these three markers were highly significant (rs597980: P=0.0057 (2,025 cases and 1,597 controls), rs6908425: P=1.57 10^-5 (3,206 cases and 4,529 controls), and rs3789604: P=3.45 10^-5 (2,823 cases and 4,066 controls)). These data increase the likelihood that ADAM33, CDKAL1, and PTPN22 are true psoriasis-risk genes.