DNA methylation signatures of bilateral hippocampal volume, asymmetry and atrophy: a cross-omics analysis in the general population
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Le résumé fourni par la source
BACKGROUND: Left-right hippocampal volumetric asymmetry and atrophy are implicated in neurodegenerative and neuropsychiatric disorders, yet their molecular basis in healthy adults remains poorly understood. METHODS: We conducted a meta-analysis of epigenome-wide association studies across six population-based cohorts (n = 8156; 53% women; mean age = 60.7 years) to identify DNA methylation signatures associated with left and right hippocampal volumes (LHCV, RHCV) and hippocampal asymmetry (i.e, differences between left and right volumes divided by their sums). FINDINGS: We identified five CpGs and 262 differentially methylated regions associated with LHCV, nine CpGs and 246 regions with RHCV, one CpG and 16 regions with asymmetry. Cross-omics integration uncovered 15 LHCV-related and 13 RHCV-related methylation-gene expression pairs, with five overlapping genes primarily involved in immune regulation. LHCV-specific genes were involved in cellular signalling, and Mendelian randomisation (MR) analyses supported a potential causal association between brain expression of DIP2C and increased risk of major depressive disorder. RHCV-specific genes were involved in neuronal differentiation pathways, with MR analyses suggesting that brain-tissue expression of BAIAP2, MACF1, SLC16A5, and CORO1B was associated with neuropsychiatric disorders. We also identified sex-specific patterns with hippocampal asymmetry. Notably, baseline methylation at these sites predicted hippocampal atrophy rates, explaining >10% of the variation. Associations with multiple healthy dietary patterns suggest modifiable influences on hippocampal structure. INTERPRETATION: These findings highlight distinct methylation profiles as potential biomarkers or therapeutic targets for neuropsychiatric and neurodegenerative conditions. FUNDING: Institutional funds, Federal Ministry of Education and Research of Germany, Alzheimer's Association.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- DNA methylation signatures of bilateral hippocampal volume, asymmetry and atrophy: a cross-omics analysis in the general population
- Date Crossref
- 01/06/2026
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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German Center for Neurodegenerative Diseases pays non établi dans la noticeStructure de recherche
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Boston University Department of Biostatistics pays non établi dans la noticeUniversité ou école supérieure
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Universitätsmedizin Greifswald pays non établi dans la noticeÉtablissement de santé
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NHS Lothian pays non établi dans la noticeÉtablissement de santé
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University of Edinburgh Department of Psychology pays non établi dans la noticeUniversité ou école supérieure
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Leiden University Medical Center pays non établi dans la noticeOrganisme public
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Curtin University Mathematics and Statistics pays non établi dans la noticeUniversité ou école supérieure
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New South Wales Department of Health pays non établi dans la noticeOrganisme public
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UNSW Sydney pays non établi dans la noticeUniversité ou école supérieure
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Centre for Healthy Brain Ageing pays non établi dans la noticeStructure de recherche
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Max Planck Institute for Biology of Ageing pays non établi dans la noticeOrganisation à but non lucratif
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Framingham Heart Study pays non établi dans la noticeStructure de recherche
German Center for Neurodegenerative Diseases, Department of Biostatistics — Boston University et Universitätsmedizin Greifswald, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.