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

Hum Mol Genet. 2013 Oct 1;22(19):4021-9. doi: 10.1093/hmg/ddt248. Epub 2013 Jun 4.

Abstract

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Case-Control Studies
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Neoplasm Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Protein-Serine-Threonine Kinases / genetics*
  • Receptors, Cell Surface
  • Reproducibility of Results
  • Risk Factors
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology

Substances

  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • JAZF1 protein, human
  • KIAA0319L protein, human
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Receptors, Cell Surface
  • PXK protein, human
  • Protein-Serine-Threonine Kinases