Genetic Colocalization of Expression Quantitative Trait Loci (eQTL) Mapping and GWAS in a multiethnic brain bank: An Insight into ancestry-specific Regulatory Architecture in Alzheimer’s disease

This study highlights the importance of population-stratified eQTL and colocalization analysis in identifying genetic regulatory mechanisms underlying complex diseases such as AD. The high colocalization probabilities indicate shared causal variants, supporting the functional relevance of these genes in AD risk. Our findings suggest that EHD1, TMEM68, and DEFA10P may play an ancestry-specific role in AD. For example, EHD1 gene is involved in neuronal BACE1 transcytosis which is highly relevant for AD. Similarly, TMEM68 was colocalized with chromosome-8 in brain prefrontal cortex and hypothalamus in GTEx panel. These insights contribute to a better understanding of AD genetic architecture, with potential implications for precision medicine approaches across populations. Results can be visualized via our newly-developed BRAINscape an interactive Shiny-based interface for seamless data visualization to facilitate the integrative analysis of multi-omics data.

Recommended citation: Ruhela, V., Cieza, B., Mayeux, R., Reyes-Dumeyer, D., Teich, A.F. and Tosto, G., 2025, July. Genetic Colocalization of Expression Quantitative Trait Loci (eQTL) Mapping and GWAS in a multiethnic brain bank: An Insight into ancestry-specific Regulatory Architecture in Alzheimer’s disease. In Alzheimer's Association International Conference. ALZ. doi:10.5281/zenodo.6546356.
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