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

被引：9

作者：

Xavier, Alexandre ^{[1
]}

Maltby, Vicki E. ^{[2
,3
]}

Ewing, Ewoud ^{[4
]}

Campagna, Maria Pia ^{[5
]}

Burnard, Sean M. ^{[1
]}

Tegner, Jesper N. ^{[6
,7
,8
,9
]}

Slee, Mark ^{[10
]}

Butzkueven, Helmut ^{[5
,11
]}

Kockum, Ingrid ^{[4
]}

Kular, Lara ^{[4
]}

Jokubaitis, Vilija G. ^{[5
]}

Kilpatrick, Trevor ^{[12
]}

Alfredsson, Lars ^{[4
]}

Jagodic, Maja ^{[4
]}

Ponsonby, Anne-Louise ^{[12
,13
]}

Taylor, Bruce V. ^{[14
]}

Scott, Rodney J. ^{[15
]}

Lea, Rodney A. ^{[16
]}

Lechner-Scott, Jeannette ^{[2
,3
]}

机构：

[1] Univ Newcastle, Hunter Med Res Inst, Sch Biomed Sci & Pharm, New Lambton Hts, NSW 2305, Australia

[2] Univ Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, New Lambton Hts, NSW 2305, Australia

[3] John Hunter Hosp, Dept Neurol, New Lambton Hts, NSW 2305, Australia

[4] Karolinska Univ Hosp, Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, S-17176 Stockholm, Sweden

[5] Monash Univ, Dept Neurosci, Cent Clin Sch, Melbourne, Vic 3004, Australia

[6] King Abdullah Univ Sci & Technol KAUST, Biol & Environm Sci & Engn Div, Thuwal 23955, Saudi Arabia

[7] King Abdullah Univ Sci & Technol KAUST, Comp Elect & Math Sci & Engn Div, Thuwal 23955, Saudi Arabia

[8] Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med,Unit Computat Med, L8 05, S-17176 Stockholm, Sweden

[9] Sci Life Lab, Tomtebodavagen 23A, S-17165 Solna, Sweden

[10] Flinders Univ S Australia, Coll Med & Publ Hlth, Bedford Pk, SA 5042, Australia

[11] MSBase Fdn, Melbourne, Vic 3004, Australia

[12] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic 3052, Australia

[13] Australian Natl Univ, Natl Ctr Epidemiol & Publ Hlth, Canberra, ACT 2601, Australia

[14] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas 7000, Australia

[15] John Hunter Hosp, Dept Mol Genet, Pathol North, New Lambton Hts, NSW 2305, Australia

[16] Queensland Univ Technol, Sch Biomed Sci, Ctr Genom & Personalised Hlth, Kelvin Grove, Qld 4059, Australia

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 16期

基金：

瑞典研究理事会;

关键词：

multiple sclerosis; epigenetics; methylation; epigenome-wide association studies; genetic risk; cell deconvolution; LINKAGE; EXPRESSION; MOLECULES; PACKAGE; DESIGN; BIAS;

D O I：

10.3390/ijms241612576

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 x 10-29) than known genetic risk loci (AUC = 0.72, 95% CI: 0.66-0.76, p = 9.07 x 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.

引用

页数：20

共 2 条

[1] An epigenetic signature is associated with multiple sclerosis independently of known genetic risk and is a more accurate classifier
Xavier, Alexandre
Maltby, Vicki E.
Ewing, Ewoud
Campagna, Maria Pia
Burnard, Sean M.
Tegner, Jesper N.
Slee, Mark
Butzkueven, Helmut
Kockum, Ingrid
Kular, Lara
Jokubaitis, Vilija G.
Kilpatrick, Trevor
Alfredsson, Lars
Jagodic, Maja
Ponsonby, Anne-Louise
Taylor, Bruce
Scott, Rodney J.
Lea, Rodney A.
Lechner-Scott, Jeannette
MULTIPLE SCLEROSIS JOURNAL, 2024, 30 (04) : 27 - 28
[2] Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients
Maltby, Vicki E.
Lea, Rodney A.
Graves, Moira C.
Sanders, Katherine A.
Benton, Miles C.
Tajouri, Lotti
Scott, Rodney J.
Lechner-Scott, Jeannette
SCIENTIFIC REPORTS, 2018, 8

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