Background Many autoimmune diseases share common susceptibility loci suggesting similar underlying cellular mechanisms involved in disease expression. Objectives The purpose of this investigation was to study 21 genetic variants in 14 genes that are confirmed autoimmune loci in a cohort of patients with early-onset psoriasis. Methods Patients with early-onset psoriasis (n = 750) and controls (n = 3531) were genotyped using the Sequenom® MassArray™ iPLEX Gold platform. Results We found strong evidence of association with two variants in the IL2/IL21 (rs6822844, genotypic P = 3·3 × 10-4; rs2069778, genotypic P = 7·86 × 10-4) region. Conclusions The findings, although requiring replication, suggest that IL2/IL21 may play a key role in the pathogenesis of psoriasis as well as in other diverse autoimmune diseases. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.