TY - JOUR
T1 - Identification of differential DNA methylation associated with multiple sclerosis
T2 - A family-based study
AU - Garcia-Manteiga, J. M.
AU - Clarelli, F.
AU - Bonfiglio, S.
AU - Mascia, E.
AU - Giannese, F.
AU - Barbiera, G.
AU - Guaschino, C.
AU - Sorosina, M.
AU - Santoro, S.
AU - Protti, A.
AU - Martinelli, V.
AU - Cittaro, D.
AU - Lazarevic, D.
AU - Stupka, E.
AU - Filippi, M.
AU - Esposito, F.
AU - Martinelli-Boneschi, F.
N1 - Funding Information:
Part of this work was supported by the Italian Ministry of Health - Ricerca Finalizzata [ RF-2011-02347955 ], by the Italian Ministry of Health with 5 × 1000 funds.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/7/15
Y1 - 2021/7/15
N2 - Multiple Sclerosis (MS) is caused by a still unknown interplay between genetic and environmental factors. Epigenetics, including DNA methylation, represents a model for environmental factors to influence MS risk. Twenty-six affected and 26 unaffected relatives from 8 MS multiplex families were analysed in a multicentric Italian study using MeDIP-Seq, followed by technical validation and biological replication in two additional families of differentially methylated regions (DMRs) using SeqCap Epi Choice Enrichment kit (Roche®). Associations from MeDIP-Seq across families were combined with aggregation statistics, yielding 162 DMRs at FDR ≤ 0.1. Technical validation and biological replication led to 2 hypo-methylated regions, which point to NTM and BAI3 genes, and to 2 hyper-methylated regions in PIK3R1 and CAPN13. These 4 novel regions contain genes of potential interest that need to be tested in larger cohorts of patients.
AB - Multiple Sclerosis (MS) is caused by a still unknown interplay between genetic and environmental factors. Epigenetics, including DNA methylation, represents a model for environmental factors to influence MS risk. Twenty-six affected and 26 unaffected relatives from 8 MS multiplex families were analysed in a multicentric Italian study using MeDIP-Seq, followed by technical validation and biological replication in two additional families of differentially methylated regions (DMRs) using SeqCap Epi Choice Enrichment kit (Roche®). Associations from MeDIP-Seq across families were combined with aggregation statistics, yielding 162 DMRs at FDR ≤ 0.1. Technical validation and biological replication led to 2 hypo-methylated regions, which point to NTM and BAI3 genes, and to 2 hyper-methylated regions in PIK3R1 and CAPN13. These 4 novel regions contain genes of potential interest that need to be tested in larger cohorts of patients.
KW - Autoimmune diseases
KW - Epigenetics
KW - Familial multiple sclerosis
KW - Genomics
KW - Methylation
KW - Multiple sclerosis
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U2 - 10.1016/j.jneuroim.2021.577600
DO - 10.1016/j.jneuroim.2021.577600
M3 - Article
AN - SCOPUS:85105575048
SN - 0165-5728
VL - 356
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
M1 - 577600
ER -