Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

作者：Tsoi Lam C; Stuart Philip E; Tian Chao; Gudjonsson Johann E; Das Sayantan; Zawistowski Matthew; Ellinghaus Eva; Barker Jonathan N; Chandran Vinod; Dand Nick; Duffin Kristina Callis; Enerback Charlotta; Esko Tonu; Franke Andre; Gladman Dafna D; Hoffmann Per; Kingo Kulli; Koks Sulev; Krueger Gerald G; Lim Henry W; Metspalu Andres; Mrowietz Ulrich; Mucha Soren; Rahman Proton; Reis Andre; Tejasvi Trilokraj; Trembath Richard; Voorhees John J; Weidinger Stephan; Weichenthal Michael

来源：Nature Communications, 2017, 8(1): 15382.

DOI：10.1038/ncomms15382

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFkB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8(+) T-cells and CD4(+) T-cells including T(H)0, T(H)1 and T(H)17). The identified loci explain similar to 28% of the genetic heritability and generate a discriminatory genetic risk score (AUC = 0.76 in our sample) that is significantly correlated with age at onset (p = 2 x 10(-89)). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

• 出版日期2017-5-24