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


Journal

Journal of neuroimmunology
ISSN: 1872-8421
Titre abrégé: J Neuroimmunol
Pays: Netherlands
ID NLM: 8109498

Informations de publication

Date de publication:
15 07 2021
Historique:
received: 09 02 2021
revised: 20 04 2021
accepted: 27 04 2021
pubmed: 16 5 2021
medline: 8 9 2021
entrez: 15 5 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 33991750
pii: S0165-5728(21)00127-2
doi: 10.1016/j.jneuroim.2021.577600
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

577600

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

J M Garcia-Manteiga (JM)

Centre for Omics Sciences, San Raffaele Scientific Institute IRCCS, Milan, Italy.

F Clarelli (F)

Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Italy.

S Bonfiglio (S)

Centre for Omics Sciences, San Raffaele Scientific Institute IRCCS, Milan, Italy.

E Mascia (E)

Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Italy.

F Giannese (F)

Centre for Omics Sciences, San Raffaele Scientific Institute IRCCS, Milan, Italy.

G Barbiera (G)

Centre for Omics Sciences, San Raffaele Scientific Institute IRCCS, Milan, Italy.

C Guaschino (C)

Department of Neurology, Sant'Antonio Abate Hospital, Gallarate, Italy.

M Sorosina (M)

Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Italy.

S Santoro (S)

Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Italy.

A Protti (A)

Ospedale Niguarda, Department of Neurology, Milan, Italy.

V Martinelli (V)

Neurology Unit, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.

D Cittaro (D)

Centre for Omics Sciences, San Raffaele Scientific Institute IRCCS, Milan, Italy.

D Lazarevic (D)

Centre for Omics Sciences, San Raffaele Scientific Institute IRCCS, Milan, Italy.

E Stupka (E)

Centre for Omics Sciences, San Raffaele Scientific Institute IRCCS, Milan, Italy.

M Filippi (M)

Neurology Unit, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy; Vita-Salute San Raffaele University, Via Olgettina 48, 20132 Milan, Italy; Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy; Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.

F Esposito (F)

Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Italy; Neurology Unit, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.

F Martinelli-Boneschi (F)

Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Italy; Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy; Neurology Unit and MS Centre, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy. Electronic address: filippo.martinelli@unimi.it.

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