Identification of differential DNA methylation associated with multiple sclerosis: A family-based study

Area of Science:

• Neuroimmunology
• Epigenetics
• Genetics

Background:

• Multiple Sclerosis (MS) etiology involves complex genetic and environmental interactions.
• Epigenetic mechanisms, such as DNA methylation, are proposed mediators of environmental influences on MS susceptibility.
• Understanding these epigenetic modifications is crucial for elucidating MS pathogenesis.

Purpose of the Study:

• To investigate DNA methylation patterns in families with a history of Multiple Sclerosis.
• To identify differentially methylated regions (DMRs) associated with MS in familial cohorts.
• To pinpoint novel genes potentially involved in MS risk through epigenetic alterations.

Main Methods:

• Utilized Methylated DNA Immunoprecipitation and Sequencing (MeDIP-Seq) in 8 Italian MS multiplex families.
• Performed technical validation and biological replication of identified DMRs in two additional families.
• Employed SeqCap Epi Choice Enrichment kit for targeted methylation analysis.

Main Results:

• Identified 162 DMRs across families with a False Discovery Rate (FDR) ≤ 0.1.
• Validated and replicated 4 novel regions: 2 hypo-methylated (NTM, BAI3 genes) and 2 hyper-methylated (PIK3R1, CAPN13 genes).
• These regions harbor genes with potential relevance to MS.

Conclusions:

• Identified novel DNA methylation patterns associated with Multiple Sclerosis in familial settings.
• The genes NTM, BAI3, PIK3R1, and CAPN13 represent potential targets for future MS research.
• Further investigation in larger patient cohorts is warranted to confirm the role of these epigenetic findings in MS.