Unlocking the Genetic Secrets of Alzheimer’s: A Key to Early Diagnosis

Published on June 21, 2023

Unlocking the secrets of Alzheimer’s disease is like unraveling a complex puzzle. Scientists have long identified genetic variants associated with AD, but understanding their significance has been challenging due to the strong linkage between these variants. To tackle this issue, researchers turned to transcriptome-wide association studies (TWAS) and employed the Joint-Tissue Imputation (JTI) approach in conjunction with Mendelian Randomization (MR). By integrating multiple datasets, they were able to identify 415 AD-associated genes, which were further narrowed down to 36 highly reliable genes, including APOC1, CR1, ERBB2, and RIN3. These genes play crucial roles in antigen processing and presentation, amyloid-beta formation, tau protein binding, and response to oxidative stress. The discovery of these genes not only enhances our understanding of AD’s underlying mechanisms but also provides potential biomarkers for early diagnosis. To delve deeper into this groundbreaking research and its implications for Alzheimer’s disease, read the full article!

Numerous genetic variants associated with Alzheimer’s disease (AD) have been identified through genome-wide association studies (GWAS), but their interpretation is hindered by the strong linkage disequilibrium (LD) among the variants, making it difficult to identify the causal variants directly. To address this issue, the transcriptome-wide association study (TWAS) was employed to infer the association between gene expression and a trait at the genetic level using expression quantitative trait locus (eQTL) cohorts. In this study, we applied the TWAS theory and utilized the improved Joint-Tissue Imputation (JTI) approach and Mendelian Randomization (MR) framework (MR-JTI) to identify potential AD-associated genes. By integrating LD score, GTEx eQTL data, and GWAS summary statistic data from a large cohort using MR-JTI, a total of 415 AD-associated genes were identified. Then, 2873 differentially expressed genes from 11 AD-related datasets were used for the Fisher test of these AD-associated genes. We finally obtained 36 highly reliable AD-associated genes, including APOC1, CR1, ERBB2, and RIN3. Moreover, the GO and KEGG enrichment analysis revealed that these genes are primarily involved in antigen processing and presentation, amyloid-beta formation, tau protein binding, and response to oxidative stress. The identification of these potential AD-associated genes not only provides insights into the pathogenesis of AD but also offers biomarkers for early diagnosis of the disease.

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