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Publications

Journal Article Ahead of print

PubMed: 42479015 DOI: 10.1177/13524585261462517

DNA methylation partially mediates the associations of Mediterranean diet scores with MS onset-risk: Results from the Ausimmune case-control study.

Mult Scler

Authors: Mehari Woldemariam Merid, Alex Eisner, Daniel J Park, Sam Tanner, Ingrid van der Mei, Vicki E Maltby, Bruce V Taylor, Jeannette Lechner-Scott, Rodney J Scott, Sarah M Thomson, Simon A Broadley, Ellen Morwitch, Trevor J Kilpatrick, Anne-Louise Ponsonby, Steve Simpson-Yap

Affiliations

  • The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
  • Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
  • Melbourne Bioinformatics, The University of Melbourne, Parkville, VIC, Australia.
  • Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, VIC, Australia.
  • The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia. Melbourne Bioinformatics, The University of Melbourne, Parkville, VIC, Australia. Murdoch Children's Research Institute, The University of Melbourne, Parkville, VIC, Australia.
  • MS Research Flagship, Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
  • School of Medicine and Public Health, Newcastle University, Callaghan, NSW, Australia.
  • Hunter Medical Research Institute, Newcastle University, Callaghan, NSW, Australia.
  • Department of Neurology, John Hunter Hospital, New Lambton Heights, NSW, Australia.
  • School of Biomedical Sciences and Pharmacy, Newcastle University, Callaghan, NSW, Australia.
  • School of Medicine and Dentistry, Griffith University, Southport, QLD, Australia.
  • Murdoch Children's Research Institute, The University of Melbourne, Parkville, VIC, Australia.
  • The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia. MS Research Flagship, Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia. Neuroepidemiology Unit, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC, Australia.

Abstract

BACKGROUND

Diet intake has been implicated in multiple sclerosis (MS) risk; however, the mechanisms are unclear.

OBJECTIVE

Investigated whether DNA methylation (DNAm) mediated the associations of diet and MS onset-risk.

METHODS

We utilised data from the Ausimmune case-control study, comparing 201 MS cases and 342 matched controls. Diet scores were estimated from food frequency questionnaires. Genotypes and DNAm were measured using the Illumina Global Screening Array and MethylationEPIC BeadChip, respectively. The 2432 top-ranked MS-associated cytosine-guanine pairs (CpGs) were dimension-reduced using Weighted-Gene Correlation Network Analysis (WGCNA) to five (A1-A5) DNAm module scores. Diet-MS associations were evaluated using multivariable logistic regression, and mediation through DNAm modules by counterfactual mediation analysis. We conducted stratified analyses by human leukocyte antigen (HLA) genotypes.

RESULTS

The alternate Mediterranean diet score (aMED) including unprocessed red meat (aMED-Red) (adjusted odds ratio (aOR) = 0.88; 95% confidence interval (CI) = 0.79-0.98) and Healthy diet scores (aOR = 0.86; 95% CI = 0.75-0.98) were associated with lower MS onset-risk. A5 DNAm module significantly mediated the associations of aMED (30.3%; p = 0.027) and aMED-Red (22.1%; p = 0.037) scores with MS onset-risk. Stratified by HLA genotypes, no differences in diet-MS associations or A5 DNAm-module mediation were seen.

CONCLUSION

Up to one-third of the associations of Mediterranean diet scores with MS onset-risk were explained by DNAm in genes involved in immune function. These findings provide a better understanding of the underlying MS pathogenesis and inform future research.

MeSH

Genes, Multiple Sclerosis, Case-Control Studies, Diet, Mediterranean, Diet, Dna Methylation, Demyelinating Diseases, Genotype, Dna, Negotiating