Dataset Information

Integrating multi-omics data to reveal the effect of genetic variant rs6430538 on Alzheimer's disease risk.

ABSTRACT:

Introduction

Growing evidence highlights a potential genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD); however, the role of the PD risk variant rs6430538 in AD remains unclear.

Methods

In Stage 1, we investigated the risk associated with the rs6430538 C allele in seven large-scale AD genome-wide association study (GWAS) cohorts. In Stage 2, we performed expression quantitative trait loci (eQTL) analysis to calculate the cis-regulated effect of rs6430538 on TMEM163 in both AD and neuropathologically normal samples. Stage 3 involved evaluating the differential expression of TMEM163 in 4 brain tissues from AD cases and controls. Finally, in Stage 4, we conducted a transcriptome-wide association study (TWAS) to identify any association between TMEM163 expression and AD.

Results

The results showed that genetic variant rs6430538 C allele might increase the risk of AD. eQTL analysis revealed that rs6430538 up-regulated TMEM163 expression in AD brain tissue, but down-regulated its expression in normal samples. Interestingly, TMEM163 showed differential expression in entorhinal cortex (EC) and temporal cortex (TCX). Furthermore, the TWAS analysis indicated strong associations between TMEM163 and AD in various tissues.

Discussion

In summary, our findings suggest that rs6430538 may influence AD by regulating TMEM163 expression. These discoveries may open up new opportunities for therapeutic strategies targeting AD.

SUBMITTER: Qiu S

PROVIDER: S-EPMC10982421 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Integrating multi-omics data to reveal the effect of genetic variant rs6430538 on Alzheimer's disease risk.

Qiu Shizheng S Sun Meili M Xu Yanwei Y Hu Yang Y

Frontiers in neuroscience 20240318

<h4>Introduction</h4>Growing evidence highlights a potential genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD); however, the role of the PD risk variant rs6430538 in AD remains unclear.<h4>Methods</h4>In Stage 1, we investigated the risk associated with the rs6430538 C allele in seven large-scale AD genome-wide association study (GWAS) cohorts. In Stage 2, we performed expression quantitative trait loci (eQTL) analysis to calculate the cis-regulated effect of rs643053 ...[more]

PMID: 38562299

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Dataset Information

Integrating multi-omics data to reveal the effect of genetic variant rs6430538 on Alzheimer's disease risk.

Introduction

Methods

Results

Discussion

Publications

Integrating multi-omics data to reveal the effect of genetic variant rs6430538 on Alzheimer's disease risk.

Similar Datasets

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