DNA Methylation Signatures of Multiple Sclerosis Occur Independently of Known Genetic Risk and Are Primarily Attributed to B Cells and Monocytes.

Xavier A, Maltby VE, Ewing E, Campagna MP, Burnard SM, Tegner JN, Slee M, Butzkueven H, Kockum I, Kular L, Jokubaitis VG, Kilpatrick T, Alfredsson L, Jagodic M, Ponsonby AL, Taylor BV, Scott RJ, Lea RA, Lechner-Scott J

Int J Mol Sci 24 (16) - [2023-08-08; online 2023-08-08]

Epigenetic mechanisms can regulate how DNA is expressed independently of sequence and are known to be associated with various diseases. Among those epigenetic mechanisms, DNA methylation (DNAm) is influenced by genotype and the environment, making it an important molecular interface for studying disease etiology and progression. In this study, we examined the whole blood DNA methylation profiles of a large group of people with (pw) multiple sclerosis (MS) compared to those of controls. We reveal that methylation differences in pwMS occur independently of known genetic risk loci and show that they more strongly differentiate disease (AUC = 0.85, 95% CI 0.82-0.89, p = 1.22 × 10-29) than known genetic risk loci (AUC = 0.72, 95% CI: 0.66-0.76, p = 9.07 × 10-17). We also show that methylation differences in MS occur predominantly in B cells and monocytes and indicate the involvement of cell-specific biological pathways. Overall, this study comprehensively characterizes the immune cell-specific epigenetic architecture of MS.

NGI SNP genotyping [Service]

NGI Uppsala (SNP&SEQ Technology Platform) [Service]

National Genomics Infrastructure [Service]

PubMed 37628757

DOI 10.3390/ijms241612576

Crossref 10.3390/ijms241612576

pmc: PMC10454485
pii: ijms241612576

Publications 9.5.0