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Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF‐AD study

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Název: Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF‐AD study
Autoři: Smith, Rebecca G., Pishva, Ehsan, Kouhsar, Morteza, Imm, Jennifer, Dobricic, Valerija, Johannsen, Peter, Wittig, Michael, Franke, Andre, Vandenberghe, Rik, Schaeverbeke, Jolien, Freund-Levi, Yvonne, Froelich, Lutz, Scheltens, Philip, Teunissen, Charlotte E., Frisoni, Giovanni, Blin, Olivier, Richardson, Jill C., Bordet, Regis, Engelborghs, Sebastiaan, de Roeck, Ellen, Martinez-Lage, Pablo, Altuna, Miren, Tainta, Mikel, Lleo, Alberto, Sala, Isabel, Popp, Julius, Peyratout, Gwendoline, Winchester, Laura, Nevado-Holgado, Alejo, Verhey, Frans, Tsolaki, Magda, Andreasson, Ulf, Blennow, Kaj, Zetterberg, Henrik, Streffer, Johannes, Vos, Stephanie J.B., Lovestone, Simon, Visser, Pieter Jelle, Bertram, Lars, Lunnon, Katie
Přispěvatelé: Universitat Autònoma de Barcelona, R&D centraal, Neuroprotection & Neuromodulation, Clinical sciences, Neurology, Université de Lille, LillOA
Zdroj: Alzheimers Dement
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Alzheimer's & dementia, vol. 20, no. 10, pp. 6722-6739
Alzheimer's & dementia
Informace o vydavateli: Wiley, 2024.
Rok vydání: 2024
Témata: Male, Neurofilament light (NfL), Methylation quantitative trait loci (mQTL), Neurofilament Proteins, neurofilament light (NfL), tau, BRAIN, DNA methylation, Cerebrospinal fluid (CSF), Genome-wide association study (GWAS), DEMENTIA, METHYLATION, amyloid, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Blood, mild cognitive impairment (MCI), Alzheimer's disease (AD), epigenome-wide association study (EWAS), biomarker, Epigenetics, Female, Life Sciences & Biomedicine, Neurovetenskaper, DNA Methylation/genetics, PACKAGE, Research Article, Chitinase-3-Like Protein 1/cerebrospinal fluid, Amyloid, YKL-40, Clinical Neurology, BETA, cerebrospinal fluid (CSF), DIAGNOSIS, methylation quantitative trait loci (mQTL), epigenome‐wide association study (EWAS), blood, Alzheimer Disease, Humans, Alzheimer Disease/genetics, Alzheimer Disease/blood, Alzheimer Disease/cerebrospinal fluid, Chitinase-3-Like Protein 1/genetics, Chitinase-3-Like Protein 1/blood, Biomarkers/cerebrospinal fluid, Biomarkers/blood, Neurofilament Proteins/cerebrospinal fluid, Neurofilament Proteins/blood, Aged, Genome-Wide Association Study, YKL‐40, epigenetics, genome‐wide association study (GWAS), protein quantitative trait loci (pQTL), Chitinase-3-Like Protein 1, METAANALYSIS, Protein quantitative trait loci (pQTL), Science & Technology, IDENTIFICATION, Neurosciences, 3202 Clinical sciences, 1103 Clinical Sciences, Biomarker, genome-wide association study (GWAS), DNA Methylation, NEUROGRANIN, Geriatrics, 5202 Biological psychology, 3209 Neurosciences, Epigenome-wide association study (EWAS), Human medicine, Neurosciences & Neurology, TAU, Tau, NEUROPATHOLOGY, 1109 Neurosciences, Mild cognitive impairment (MCI), Biomarkers
Popis: INTRODUCTIONWe investigated blood DNA methylation patterns associated with 15 well‐established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration.METHODSWe assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF‐AD) study using the EPIC array.RESULTSWe 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.DISCUSSIONWe 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.
Druh dokumentu: Article
Other literature type
Popis souboru: application/pdf
Jazyk: English
ISSN: 1552-5279
1552-5260
DOI: 10.1002/alz.14098
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39193893
https://serval.unil.ch/resource/serval:BIB_8DB8DBD5DA45.P001/REF.pdf
https://serval.unil.ch/notice/serval:BIB_8DB8DBD5DA45
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_8DB8DBD5DA452
https://repository.uantwerpen.be/docstore/d:irua:25710
https://hdl.handle.net/10067/2087850151162165141
https://biblio.vub.ac.be/vubir/blood-dna-methylomic-signatures-associated-with-csf-biomarkers-of-alzheimers-disease-in-the-emifad-study(1759a547-2aa6-472d-85b1-6a3d0b2aed2b).html
http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-115683
Rights: CC BY
Přístupové číslo: edsair.doi.dedup.....b2f8cba0412dc7644a2b18647e6b4a0d
Databáze: OpenAIRE
Popis
Abstrakt:INTRODUCTIONWe investigated blood DNA methylation patterns associated with 15 well‐established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration.METHODSWe assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF‐AD) study using the EPIC array.RESULTSWe 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.DISCUSSIONWe 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.
ISSN:15525279
15525260
DOI:10.1002/alz.14098