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Updated: Sep 27, 2025

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
Machine learning methods applied to genotyping data capture interactions between single nucleotide variants in late
Magdalena Arnal Segura1,2,3, Giorgio Bini2, Dietmar Fernandez Orth3
1Department of Biology "Charles Darwin" Sapienza University of Rome Rome Italy.
Introduction:
Genome-wide association studies (GWAS) in late onset Alzheimer's disease (LOAD) provide lists of individual genetic determinants. However, GWAS do not capture the synergistic effects among multiple genetic variants and lack good specificity.
Methods:
We applied tree-based machine learning algorithms (MLs) to discriminate LOAD (>700 individuals) and age-matched unaffected subjects in UK Biobank with single nucleotide variants (SNVs) from Alzheimer's disease (AD) studies, obtaining specific genomic profiles with the prioritized SNVs.
Results:
MLs prioritized a set of SNVs located in genes PVRL2, TOMM40, APOE, and APOC1, also influencing gene expression and splicing. The genomic profiles in this region showed interaction patterns involving rs405509 and rs1160985, also present in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. rs405509 located in APOE promoter interacts with rs429358 among others, seemingly neutralizing their predisposing effect.
Discussion:
Our approach efficiently discriminates LOAD from controls, capturing genomic profiles defined by interactions among SNVs in a hot-spot region.
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