Faculty, Staff and Student Publications
Publication Date
3-9-2025
Abstract
Genetic variants increase the risk of neurocognitive disorders in later life, including vascular dementia (VaD) and Alzheimer's disease (AD), but the precise relationships between genetic risk factors and underlying disease etiologies are not well understood. Transcriptome-wide association studies (TWASs) can be leveraged to better characterize the genes and biological pathways underlying genetic influences on disease. To date, almost all existing TWASs on VaD and AD have been conducted using expression studies from individuals of a single genetic ancestry, primarily European. Using the joint likelihood-based inference framework in Multi-ancEstry TRanscriptOme-wide analysis (METRO), we leveraged gene expression data from European ancestry (EA) and African ancestry (AA) samples to identify genes associated with general cognitive function, white matter hyperintensity (WMH), and AD. Regions were fine-mapped using Fine-mapping Of CaUsal gene Sets (FOCUS). We identified 266, 23, 69, and 2 genes associated with general cognitive function, WMH, AD (using EA GWAS summary statistics), and AD (using AA GWAS), respectively (Bonferroni-corrected alpha =
Keywords
Aged, Female, Humans, Male, Alzheimer Disease, Black People, Cognition, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Transcriptome, White Matter, White People
DOI
10.3390/ijms26062443
PMID
40141087
PMCID
PMC11942532
PubMedCentral® Posted Date
3-9-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons