Haplotype-Resolved DNA Methylation at the <i>APOE</i> Locus identifies Allele-Specific Epigenetic Signatures Relevant to Alzheimer's Disease Risk.

ABSTRACT: The APOE gene encodes a key lipid transport protein and plays a central role in Alzheimer's disease (AD) pathogenesis. Three common APOE alleles, ε2 (rs7412(C>T), ε3 (reference), and ε4 (rs429358(T>C)), arise from two coding variants in exon 4 and confer distinct AD risk profiles, with ε4 increasing risk and ε2 providing protection. The ε3-linked APOE variant rs769455[T] has also been associated with elevated AD risk in individuals of African ancestry carrying both rs769455[T] and ε4 alleles. These single nucleotide variants (SNVs) reside in a cytosine-phosphate-guanine (CpG) island, which is a region with a higher frequency of CpG sites compared to the rest of the genome. CpG sites are subject to 5-methylcytosine (5mC) methylation by DNA methyltransferases which add a

SUBMITTER: Genner RM 

PROVIDER: S-EPMC12236645 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature