{"doi":"10.1002/alz.14098","title":"Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF‐AD study","abstract":"INTRODUCTION: We investigated blood DNA methylation patterns associated with 15 well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration. METHODS: We assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF-AD) study using the EPIC array. RESULTS: We identified Bonferroni-significant differential methylation associated with CSF YKL-40 (five loci) and neurofilament light chain (NfL; seven loci) levels, with two of the loci associated with CSF YKL-40 levels correlating with plasma YKL-40 levels. A co-localization analysis showed shared genetic variants underlying YKL-40 DNA methylation and CSF protein levels, with evidence that DNA methylation mediates the association between genotype and protein levels. Weighted gene correlation network analysis identified two modules of co-methylated loci correlated with several amyloid measures and enriched in pathways associated with lipoproteins and development. DISCUSSION: We conducted the most comprehensive epigenome-wide association study (EWAS) of AD-relevant CSF biomarkers to date. Future work should explore the relationship between YKL-40 genotype, DNA methylation, and protein levels in the brain. HIGHLIGHTS: Blood DNA methylation was assessed in the EMIF-AD MBD study. Epigenome-wide association studies (EWASs) were performed for 15 Alzheimer's disease (AD)-relevant cerebrospinal fluid (CSF) biomarker measures. Five Bonferroni-significant loci were associated with YKL-40 levels and seven with neurofilament light chain (NfL). DNA methylation in YKL-40 co-localized with previously reported genetic variation. DNA methylation potentially mediates the effect of single-nucleotide polymorphisms (SNPs) in YKL-40 on CSF protein levels.","journal":"Alzheimer s & Dementia","year":2024,"id":431750,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6103,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":284876,"name":"Ehsan Pishva","orcid":"0000-0002-8964-0682","position":1,"is_corresponding":false},{"id":1235023,"name":"Morteza Kouhsar","orcid":"0000-0001-6092-3016","position":2,"is_corresponding":false},{"id":1236000,"name":"Jennifer Imm","orcid":"0000-0002-8827-8669","position":3,"is_corresponding":false},{"id":7732,"name":"Valerija Dobričić","orcid":"0000-0001-8559-1097","position":4,"is_corresponding":false},{"id":840254,"name":"Peter Johannsen","orcid":"0000-0002-0528-1070","position":5,"is_corresponding":false},{"id":1236001,"name":"Michael Wittig","orcid":"0000-0003-4240-4356","position":6,"is_corresponding":false},{"id":210855,"name":"Andre Franke","orcid":null,"position":7,"is_corresponding":false},{"id":65635,"name":"Rik Vandenberghe","orcid":"0000-0001-6237-2502","position":8,"is_corresponding":false},{"id":302520,"name":"Jolien Schaeverbeke","orcid":"0000-0003-2257-0568","position":9,"is_corresponding":false},{"id":463085,"name":"Yvonne Freund‐Levi","orcid":"0000-0001-6863-6679","position":10,"is_corresponding":false},{"id":67594,"name":"Lutz Frölich","orcid":null,"position":11,"is_corresponding":false},{"id":226631,"name":"Philip Scheltens","orcid":"0000-0002-1046-6408","position":12,"is_corresponding":false},{"id":242552,"name":"Charlotte E. Teunissen","orcid":"0000-0002-4061-0837","position":13,"is_corresponding":false},{"id":289186,"name":"Giovanni B. Frisoni","orcid":"0000-0001-7075-7082","position":14,"is_corresponding":false},{"id":303520,"name":"Olivier Blin","orcid":null,"position":15,"is_corresponding":false},{"id":302523,"name":"Jill Richardson","orcid":"0000-0001-6564-3187","position":16,"is_corresponding":false},{"id":302524,"name":"Régis Bordet","orcid":"0000-0003-3916-6422","position":17,"is_corresponding":false},{"id":17459,"name":"Sebastiaan Engelborghs","orcid":"0000-0003-0304-9785","position":18,"is_corresponding":false},{"id":831919,"name":"Ellen De Roeck","orcid":"0000-0002-6566-6562","position":19,"is_corresponding":false},{"id":226617,"name":"Pablo Martínez‐Lage","orcid":"0000-0001-5404-9967","position":20,"is_corresponding":false},{"id":232598,"name":"Miren Altuna","orcid":"0000-0001-9709-5314","position":21,"is_corresponding":false},{"id":226635,"name":"Mikel Tainta","orcid":"0000-0003-0624-1211","position":22,"is_corresponding":false},{"id":27613,"name":"Alberto Lleó","orcid":"0000-0002-2568-5478","position":23,"is_corresponding":false},{"id":302528,"name":"Isabel Sala","orcid":"0000-0002-9886-4792","position":24,"is_corresponding":false},{"id":242547,"name":"Julius Popp","orcid":"0000-0002-0068-0312","position":25,"is_corresponding":false},{"id":303521,"name":"Gwendoline Peyratout","orcid":null,"position":26,"is_corresponding":false},{"id":1018668,"name":"Laura Winchester","orcid":"0000-0003-3826-7694","position":27,"is_corresponding":false},{"id":638239,"name":"Alejo Nevado‐Holgado","orcid":"0000-0001-9276-2720","position":28,"is_corresponding":false},{"id":852005,"name":"Frans Verhey","orcid":null,"position":29,"is_corresponding":false},{"id":242545,"name":"Magda Tsolaki","orcid":"0000-0002-2072-8010","position":30,"is_corresponding":false},{"id":302519,"name":"Ulf Andréasson","orcid":"0000-0001-8622-052X","position":31,"is_corresponding":false},{"id":27600,"name":"Kaj Blennow","orcid":"0000-0002-1890-4193","position":32,"is_corresponding":false},{"id":242553,"name":"Henrik Zetterberg","orcid":"0000-0002-4671-6763","position":33,"is_corresponding":false},{"id":242550,"name":"Johannes Streffer","orcid":"0000-0002-9387-5951","position":34,"is_corresponding":false},{"id":302518,"name":"Stephanie J. B. Vos","orcid":"0000-0002-2045-9818","position":35,"is_corresponding":false},{"id":67552,"name":"Simon Lovestone","orcid":null,"position":36,"is_corresponding":false},{"id":242554,"name":"Pieter Jelle Visser","orcid":"0000-0001-8008-9727","position":37,"is_corresponding":false},{"id":242548,"name":"Lars Bertram","orcid":"0000-0002-0108-124X","position":38,"is_corresponding":false},{"id":92329,"name":"Katie Lunnon","orcid":"0000-0001-7570-6065","position":39,"is_corresponding":false},{"id":284875,"name":"Rebecca G. Smith","orcid":"0000-0001-9264-1056","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:59:30.747263Z","pmid":"39193893","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}