Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
DNA methylation partially mediates the associations of Mediterranean diet scores with MS onset-risk: Results from the Ausimmune case-control study.
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Merid Mehari Woldemariam, Eisner Alex, Park Daniel J, Tanner Sam, van der Mei Ingrid, Maltby Vicki E, Taylor Bruce V, Lechner-Scott Jeannette, Scott Rodney J, Thomson Sarah M, Broadley Simon A, Morwitch Ellen, Kilpatrick Trevor J, Ponsonby Anne-Louise, Simpson-Yap Steve, Ausimmune Investigators Group
Аннотация
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.
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.