A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

作者：Martin Jose Ezequiel^*; Assassi Shervin; Diaz Gallo Lina Marcela; Broen Jasper C; Simeon Carmen P; Castellvi Ivan; Vicente Rabaneda Esther; Fonollosa Vicente; Ortego Centeno Norberto; Gonzalez Gay Miguel A; Espinosa Gerard; Carreira Patricia; Camps Mayte; Sabio Jose M; D' alfonso Sandra; Vonk Madelon C; Voskuyl Alexandre E; Schuerwegh Annemie J; Kreuter Alexander; Witte Torsten; Riemekasten Gabriella; Hunzelmann Nicolas; Airo Paolo; Beretta Lorenzo

来源：Human Molecular Genetics, 2013, 22(19): 4021-4029.

DOI：10.1093/hmg/ddt248

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 x 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 x 10(-11), OR = 1.20) and JAZF1 (P = 1.11 x 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

• 出版日期2013-10-1