GG-09 A role for EBNA2 in mechanisms that are responsible for lupus and other autoimmune diseases

Abstract

Background Explaining the genetics of many diseases is challenging because most associations localize to incompletely understood regulatory regions. Methods We show that transcription factors (TFs) occupy multiple loci of individual complex genetic disorders much more than expected by chance using novel computational methods. Results Application to 213 phenotypes and 1,544 TF binding datasets identifies 2,264 relationships between hundreds of TFs and 94 phenotypes, including AR in prostate cancer and GATA3 in breast cancer. Strikingly, nearly half of the systemic lupus erythematosus risk loci are occupied by the Epstein-Barr virus (EBV) Nuclear Antigen 2 (EBNA2) protein (OR=6, P Conclusions Our results nominate mechanisms that operate across risk loci within disease phenotypes; they suggest new paradigms for disease origin and strongly support a role for Epstein-Barr virus in the generation of systemic lupus erythematosus, as well as of particular other autoimmune diseases, apparently related to lupus by the genomic mechanisms that produce them.