Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 08 2022
09 08 2022
Historique:
received:
03
09
2021
accepted:
25
07
2022
entrez:
9
8
2022
pubmed:
10
8
2022
medline:
12
8
2022
Statut:
epublish
Résumé
Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health.
Identifiants
pubmed: 35945220
doi: 10.1038/s41467-022-32319-8
pii: 10.1038/s41467-022-32319-8
pmc: PMC9363452
doi:
Substances chimiques
Biomarkers
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4670Subventions
Organisme : Wellcome Trust
ID : 108890/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104036/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 225442/Z/22/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221890/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 220857/Z/20/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17215
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S010351/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/W002566/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/W002388/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R024065/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17209
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CS/15/5/
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG054628
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH124873
Pays : United States
Organisme : Chief Scientist Office
ID : CZD/16/6
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/W008793/1
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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