Whole genome methylation sequencing in blood identifies extensive differential DNA methylation in late-onset dementia due to Alzheimer's disease.
Alzheimers Dement
; 20(2): 1050-1062, 2024 Feb.
Article
de En
| MEDLINE
| ID: mdl-37856321
ABSTRACT
INTRODUCTION:
DNA microarray-based studies report differentially methylated positions (DMPs) in blood between late-onset dementia due to Alzheimer's disease (AD) and cognitively unimpaired individuals, but interrogate < 4% of the genome.METHODS:
We used whole genome methylation sequencing (WGMS) to quantify DNA methylation levels at 25,409,826 CpG loci in 281 blood samples from 108 AD and 173 cognitively unimpaired individuals.RESULTS:
WGMS identified 28,038 DMPs throughout the human methylome, including 2707 differentially methylated genes (e.g., SORCS3, GABA, and PICALM) encoding proteins in biological pathways relevant to AD such as synaptic membrane, cation channel complex, and glutamatergic synapse. One hundred seventy-three differentially methylated blood-specific enhancers interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD.DISCUSSION:
WGMS identifies differentially methylated CpGs in known and newly detected genes and enhancers in blood from persons with and without AD. HIGHLIGHTS Whole genome DNA methylation levels were quantified in blood from persons with and without Alzheimer's disease (AD). Twenty-eight thousand thirty-eight differentially methylated positions (DMPs) were identified. Two thousand seven hundred seven genes comprise DMPs. Forty-eight of 75 independent genetic risk loci for AD have DMPs. One thousand five hundred sixty-eight blood-specific enhancers comprise DMPs, 173 of which interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Méthylation de l'ADN
/
Maladie d'Alzheimer
Limites:
Humans
Langue:
En
Journal:
Alzheimers Dement
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique