Genetic Burden and <i>APOE</i> Methylation in a Korean Multi-Generational Alzheimer's Disease Family: An Exploratory Multi-Omics Case Study.

ABSTRACT: Background/Objectives: Alzheimer's disease (AD) exhibits high heritability (60-80%), yet individual-level genetic risk prediction remains challenging. While APOE ε4 is the strongest genetic risk factor, incomplete penetrance complicates risk assessment. Methods: We analyzed seven blood-related members across three generations using the Korean Chip v2.0 genotyping (~1.2 M SNPs) and Illumina EPICv2 DNA methylation profiling. Genetic burden score (GBS) was calculated by summing risk alleles across 320 variants in six AD-associated genes (APOE, PICALM, CLU, CR1, BIN1, and ABCA7). Results: An unexpected pattern was observed in this family: the affected individual (J-003) had the lowest GBS (39 alleles), while individuals with

SUBMITTER: Eom JH 

PROVIDER: S-EPMC12941720 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature