Neuroimaging PheWAS and molecular phenotyping implicate PSMC3 in Alzheimer's disease

Area of Science:

• Neuroscience
• Genetics
• Alzheimer's Disease Research

Background:

• Neuroimaging genetics has improved Alzheimer's disease (AD) understanding.
• Functional genomics frameworks are needed to link genetic loci to neurological outcomes in AD.

Purpose of the Study:

• To explore relationships between AD-associated variants and disease.
• To investigate the impact of these variants on gene expression and neuroanatomical phenotypes.

Main Methods:

• Mapped AD genes to neuroimaging traits using the NeuroimaGene Atlas.
• Predicted AD neurological features by comparing gene-derived and clinical neuroimaging data.
• Performed genetic covariance analyses for shared architecture and dementia family history associations.

Main Results:

• Implicated PSMC3 in AD pathophysiology.
• Identified AD endophenotypes, including dementia family history.
• Linked these endophenotypes to frontal cortex thickness/volume and cerebrospinal fluid volume changes.

Conclusions:

• Prioritized AD genes associated with vulnerable brain regions.
• Provided a potential mechanistic framework for AD gene function.
• Suggested pathways for downstream functional validation in AD research.