Journal Article

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

Bowcock, Anne, Yin, Xianyong, Irwan, Ishak, Gupta, Rashmi, Liu, Jianjun, Padyukov, Leonid, Foo, Jia Nee, Teo, Yikying, Shen, Changbing, Ståhle, Mona, Zuo, Xianbo, Li, Yi, Estivill, Xavier, Catanese, Joseph J., Krueger, Gerald G., Sanchez, Fabio, Ellinghaus, Eva, Mucha, Sören, Zhang, Xuejun, Zhang, Anping, Sun, Liangdan, Weidinger, Stephan, Han, Jiali, Low, Hui Qi, Liao, Wilson, Li, Yonghong, Zhu, Caihong, Franke, Andre, Duffin, Kristina Callis, Lieb, Wolfgang, Weichenthal, Michael, Wang, Ling, Liany, Herty, Seielstad, Mark, Sim, Karseng, Qureshi, Abrar A., de Bakker, Paul I. W., Theng, Colin T. S., De Jager, Philip L.

2015

Overview

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. Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here Yin et al . conduct a large trans-ethnic genome-wide meta-analysis and identify novel loci that contribute to population-specific susceptibility.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
• Subject: 49/47 / 631/1647/2217/2138 / 692/420/2489/144 / 692/699/249/1313/1758 / Adaptor Proteins, Vesicular Transport - genetics / Asian Continental Ancestry Group - genetics / Case-Control Studies / Core Binding Factor Alpha 2 Subunit - genetics / DEAD-box RNA Helicases - genetics / European Continental Ancestry Group - genetics / Genes, MHC Class I - genetics / Genetic Predisposition to Disease / Genetics / Genome-Wide Association Study / Heterogeneity / Humanities and Social Sciences / Humans / Interferon-Induced Helicase, IFIH1 / Interleukin-12 Subunit p40 - genetics / Minority & ethnic groups / multidisciplinary / Psoriasi / Psoriasis / Psoriasis - genetics / Science / Science (multidisciplinary) / Skin diseases / Transcription Factors - genetics / Tumor Suppressor Proteins - genetics