Accurate DNA methylation predictor for C9orf72 repeat expansion alleles in the pathogenic range.

ABSTRACT: The hexanucleotide (G₄C₂) repeat expansion in the promoter region of C9orf72 is the most frequent genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In this study, we conducted a genome-wide DNA methylation (DNAm) analysis using EPIC version 2 (EPICv2) arrays on an FTD cohort comprising 27 carriers and 250 non-carriers of the pathogenic C9orf72 repeat expansion from the Amsterdam Dementia Cohort. We identified differentially methylated CpGs probes associated with the pathogenic C9orf72 expansion and used these findings to create a DNAm least absolute shrinkage and selection operator (LASSO) predictor to identify repeat expansion carriers. Eight CpG sites at the C9orf72 locus were significantly differentially hypermethylated in repe

SUBMITTER: Ramesh N 

PROVIDER: S-EPMC12552990 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature