Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.

Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.This study was funded by the Key Project of Natural Science Foundation of China (81130031, 30530670), National Basic Research/nProgram of China (973 Plan) (2012CB722404, 2007B516801), Anhui Provincial Special Scientific Program (2007-7), the National Science Fund for Excellent Young Scholars (81222022), the Outstanding Talents of Organization Department of the CPC (Communist/nParty of China) Central Committee Program, the Local Universities Characteristics and Advantages of Discipline Development Program of the Ministry of Finance of China, General Program of National Natural Science Foundation of China (81370044, 81000692,81172866, 30771196, 30800990, 81072461), High-Tech Research and Development Program of China (863 Plan) (2007AA02Z161), Anhui High Education Youth Talent Fund (X. Yin), Anhui Medical University PhD Fund (XJ201429) and the Agency for Science, Technology and Research of Singapore. Funding for the US contribution was provided in part by grants from the National Institutes of Health to W.L. (R01AR065174 and K08AR057763) and A.M.B. (R01AR050266). We thank the National Psoriasis Foundation for provision of US replication samples. The contribution from Sweden was funded through the Swedish Medical Research Council, the Psoriasis Association and/nKarolinska Institutet. The Psoriatic Arthritis and Psoriasis and Follow-up Study was supported in part by a grant from the Department of Dermatology, BWH; and the BWH PhenoGenetic project was supported in part by a grant from the Brigham Research Institute. P.L.D. is a Harry Weaver Neuroscience Scholar of National Multiple Sclerosis Society. Genotyping of samples in GAIN of GWAS stage was provided through the Genetic Association Information Network. Samples and associated phenotype data for the Collaborative Association Study of Psoriasis were provided by Gonc¸alo R. Abecasis, James T. Elder, Anne M. Bowcock, Gerald G. Krueger. The project received infrastructure/nsupport through the DFG Clusters of Excellence ‘Inflammation at Interfaces’ (grants EXC306 and EXC306/2), and was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (sysINFLAME, grant # 01ZX1306A), and the PopGen 2.0 network (01EY1103). The research of Xavier Estivill is supported by the Generalitat de Catalunya AGAUR 2014 SGR-113