Genome-Wide Assessment of Differential DNA Methylation Associated with Autoantibody Production in Systemic Lupus Erythematosus

• DOI: 10.1371/journal.pone.0129813
• Publication Date: 2015-07-20T17:52:17Z
• Authors: Sharon A. Chung; Joanne Nititham; Emon Elboudwarej; Hong L. Quach; Kimberly E. Taylor; Lisa F. Barcellos; Lindsey A. Criswell
• Keywords: CpG site

Systemic lupus erythematosus (SLE) is characterized by the development of autoantibodies associated with specific clinical manifestations. Previous studies have shown an association between differential DNA methylation and SLE susceptibility, but not investigated SLE-related autoantibodies. Our goal was to determine whether production clinically relevant autoantibodies, emphasis on anti-dsDNA autoantibody. In this study, we status 467,314 CpG sites in 326 women SLE. Using a discovery replication study design, identified replicated significant associations autoantibody 16 (pdiscovery<1.07E-07 preplication<0.0029) 11 genes. Associations were further using multivariable regression adjust for estimated leukocyte cell proportions population substructure. The adjusted mean difference positive negative cases ranged from 1.2% 19%, odds ratio comparing lowest highest tertiles 6.8 18.2. Differential these also anti-SSA, anti-Sm, anti-RNP production. Overall, hypomethylated compared cases. within major histocompatibility region strongly Genes differentially methylated represent multiple biologic pathways, been genetic studies. conclusion, hypomethylation genes different pathways anti-dsDNA, SLE, are explained variation. Thus, epigenetic mechanisms such as complementary method identify that may contribute heterogeneity autoimmune diseases.