Letter

Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus

    • 1Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08907, Spain;
    • 2Cancer Epigenetics Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08907, Spain;
    • 3Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Christian-Albrechts-University Kiel, Kiel D-24105, Germany;
    • 4Bioinformatics Department, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain;
    • 5Broad Institute, Cambridge, Massachusetts 02142, USA;
    • 6Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Brookline, Massachusetts 02115, USA;
    • 7Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, NIH, HHS, Bethesda, Maryland 20892, USA;
    • 8Division of Rheumatology, Gregorio Marañon Hospital, Madrid 28007, Spain;
    • 9ISCIII Center for Biomedical Research on Rare Diseases, Valencia 46012, Spain;
    • 10Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC), Badalona 08916, Spain;
    • 11Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, 73104, USA;
    • 12U.S. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, 73104, USA;
    • 13Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
Published December 22, 2009. https://doi.org/10.1101/gr.100289.109
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cover of Genome Research Vol 36 Issue 5
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May 2026, Vol. 36, No. 5
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Abstract

Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease.

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