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. 2023 Mar 29;8(14):13332-13341.
doi: 10.1021/acsomega.3c00696. eCollection 2023 Apr 11.

Integrative Genomic Analysis of m6a-SNPs Identifies Potential Functional Variants Associated with Alzheimer's Disease

Syed Mansoor Jan  1 , Aamir Fahira  2 , Yongyong Shi  2 , Mohammad Imran Khan  3   4 , Alam Jamal  3 , Arif Mahmood  5 , Sulaiman Shams  1 , Zahida Parveen  1 , Junjian Hu  6 , Muhammad Umair  7 , Abdul Wadood  1
Affiliations

Integrative Genomic Analysis of m6a-SNPs Identifies Potential Functional Variants Associated with Alzheimer's Disease

Syed Mansoor Jan et al. ACS Omega. .

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that affects 35 million people worldwide. However, no potential therapeutics currently are available for AD because of the multiple factors involved in it, such as regulatory factors with their candidate genes, factors associated with the expression levels of its corresponding genes, and many others. To date, 29 novel loci from GWAS have been reported for AD by the Psychiatric Genomics Consortium (PGC2). Nevertheless, the main challenge of the post-GWAS era, namely to detect significant variants of the target disease, has not been conducted for AD. N6-methyladenosine (m6a) is reported as the most prevalent mRNA modification that exists in eukaryotes and that influences mRNA nuclear export, translation, splicing, and the stability of mRNA. Furthermore, studies have also reported m6a's association with neurogenesis and brain development. We carried out an integrative genomic analysis of AD variants from GWAS and m6a-SNPs from m6AVAR to identify the effects of m6a-SNPs on AD and identified the significant variants using the statistically significance value (p-value <0.05). The cis-regularity variants with their corresponding genes and their influence on gene expression in the gene expression profiles of AD patients were determined, and showed 1458 potential m6a-SNPs (based on p-value <0.05) associated with AD. eQTL analysis showed that 258 m6a-SNPs had cis-eQTL signals that overlapped with six significant differentially expressed genes based on p-value <0.05 in two datasets of AD gene expression profiles. A follow-up study to elucidate the impact of our identified m6a-SNPs in the experimental study would validate our findings for AD, which would contribute to the etiology of AD.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Biological functions of m6a genes with GO terms.
Figure 2
Figure 2
GO molecular function and cellular components for m6a genes.
Figure 3
Figure 3
Protein–protein interactions.
Figure 4
Figure 4
Differentially expressed genes in GSE33000.
Figure 5
Figure 5
Workflow and design of the study.
See this image and copyright information in PMC

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