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Keywords = genetically regulated expression (GReX)

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13 pages, 1429 KiB  
Article
A Method for Bridging Population-Specific Genotypes to Detect Gene Modules Associated with Alzheimer’s Disease
by Yulin Dai, Peilin Jia, Zhongming Zhao and Assaf Gottlieb
Cells 2022, 11(14), 2219; https://doi.org/10.3390/cells11142219 - 16 Jul 2022
Cited by 4 | Viewed by 2698
Abstract
Background: Genome-wide association studies have successfully identified variants associated with multiple conditions. However, generalizing discoveries across diverse populations remains challenging due to large variations in genetic composition. Methods that perform gene expression imputation have attempted to address the transferability of gene discoveries across [...] Read more.
Background: Genome-wide association studies have successfully identified variants associated with multiple conditions. However, generalizing discoveries across diverse populations remains challenging due to large variations in genetic composition. Methods that perform gene expression imputation have attempted to address the transferability of gene discoveries across populations, but with limited success. Methods: Here, we introduce a pipeline that combines gene expression imputation with gene module discovery, including a dense gene module search and a gene set variation analysis, to address the transferability issue. Our method feeds association probabilities of imputed gene expression with a selected phenotype into tissue-specific gene-module discovery over protein interaction networks to create higher-level gene modules. Results: We demonstrate our method’s utility in three case-control studies of Alzheimer’s disease (AD) for three different race/ethnic populations (Whites, African descent and Hispanics). We discovered 182 AD-associated genes from gene modules shared between these populations, highlighting new gene modules associated with AD. Conclusions: Our innovative framework has the potential to identify robust discoveries across populations based on gene modules, as demonstrated in AD. Full article
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