Quantitative Trait Module-Based Genetic Analysis of Alzheimer's Disease

Area of Science:

• Neurogenetics
• Neuroimaging
• Computational Biology

Background:

• Alzheimer's Disease (AD) pathology progresses from the medial temporal lobe to other brain regions.
• Subcortical structures play a crucial role in brain function and are affected in AD.

Purpose of the Study:

• To investigate the association between genetic loci and subcortical structure volumes in Alzheimer's Disease.
• To identify both main and interactive effect loci influencing these brain structures.

Main Methods:

• Analysis of 393 samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
• Clustering of 35 subcortical brain structures into five distinct modules based on volume correlations.
• Identification of genetic loci associated with module volumes using main and interactive effect analyses.

Main Results:

• Thirty-five subcortical structures were grouped into five modules: limbic system, corpus callosum, thalamus-cerebellum-brainstem-pallidum, basal ganglia neostriatum, and ventricular system.
• Distinct Gene Ontology and KEGG enrichment patterns were observed for each module.
• Several main and interactive effect loci were identified for each module, linked to structure function, material transport, and signal transduction.

Conclusions:

• Genetic loci significantly influence the volumes of specific subcortical brain modules in Alzheimer's Disease.
• These findings highlight the complex genetic architecture underlying brain structural changes in AD.
• The identified loci provide potential targets for understanding AD pathogenesis and developing therapeutic strategies.