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The dynamics of methylation of CpG sites associated with SLE subtypes in a longitudinal cohort
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10 2022
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Source: Arthritis Rheumatol. 74(10):1676-1686
[PDF-1.11 MB]
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Alternative Title:Arthritis Rheumatol
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Personal Author:
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Description:Objective
Cross-sectional studies have revealed associations between DNA methylation and systemic lupus erythematosus (SLE) outcomes. To study the dynamics of DNA methylation, we examined participants from a SLE longitudinal cohort sampled at two time-points.
Methods
One hundred and one participants from the California Lupus Epidemiology Study were studied. DNA extracted from blood at cohort enrollment and after two years was analyzed using the Illumina EPIC BeadChip. Paired t-tests were utilized to identify changes at 256 CpG sites previously associated with SLE subtypes as well as genome-wide. Mixed linear models were developed to understand the relationship between DNA methylation and disease activity, medication use and sample cell proportions, adjusting for age, sex and genetic principal components.
Results
The majority of CpGs that were previously associated with SLE subtypes remained stable over two years (185 CpGs (72.3%), t-test FDR >0.05). Compared to background genome-wide methylation, there was an enrichment of SLE subtype associated CpGs that changed over time (27.7% vs 0.34%). Changes in cell proportion were associated with changes at 67 CpGs (p<2.70E-05) and 15 CpGs had at least one significant association with use of an immunosuppressive medication.
Conclusion
In this longitudinal cohort of SLE, we identified a subset of SLE subtype associated CpGs that were stable over time and may be useful as biomarkers of disease subtypes. Another subset of SLE subtype-associated CpGs changed at a higher proportion compared to the genome-wide methylome. Additional studies are needed to understand the etiology and impact of these methylation changes in SLE-associated CpGs.
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Pubmed ID:35635730
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Pubmed Central ID:PMC9529797
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Volume:74
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Issue:10
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