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 × 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 × 10-11, OR = 1.20) and JAZF1 (P = 1.11 × 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.
|Titolo:||A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci|
|Parole Chiave:||Case-Control Studies; Genetic Loci; Genetic Variation; Genome-Wide Association Study; Humans; Intracellular Signaling Peptides and Proteins; Lupus Erythematosus, Systemic; Neoplasm Proteins; Nerve Tissue Proteins; Nuclear Proteins; Polymorphism, Single Nucleotide; Protein-Serine-Threonine Kinases; Reproducibility of Results; Risk Factors; Scleroderma, Systemic; Genetic Predisposition to Disease; Genetics; Genetics (clinical); Molecular Biology|
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Data di pubblicazione:||2013|
|Digital Object Identifier (DOI):||10.1093/hmg/ddt248|
|Appare nelle tipologie:||01 - Articolo su periodico|