DNA methylation regulator-mediated modification patterns and risk of intracranial aneurysm: a multi-omics and epigenome-wide association study integrating machine learning, Mendelian randomization, eQTL and mQTL data

• Published in: Journal of translational medicine Vol. 21; no. 1; pp. 1 - 25
• Main Authors: Maimaiti, Aierpati, Turhon, Mirzat, Abulaiti, Aimitaji, Dilixiati, Yilidanna, Zhang, Fujunhui, Axieer, Aximujiang, Kadeer, Kaheerman, Zhang, Yisen, Maimaitili, Aisha, Yang, Xinjian
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 23.09.2023; BioMed Central; BMC
• Subjects: Algorithms; Aneurysm; Aneurysms; Anopheles; B cells; Bioinformatics; Biomarkers; Data mining; Datasets; DNA; DNA methylation; DNA methylation regulator; Environmental factors; Epigenetic inheritance; Epigenetics; Genes; Genome-wide association studies; Genomes; Genomics; Health aspects; Intracranial aneurysms; Learning algorithms; Machine learning; Mendelian randomization; Methylation; Multi-omics; Pathogenesis; Therapeutic applications; Transcriptomics
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-023-04512-w

Background Intracranial aneurysms (IAs) pose a significant and intricate challenge. Elucidating the interplay between DNA methylation and IA pathogenesis is paramount to identify potential biomarkers and therapeutic interventions. Methods We employed a comprehensive bioinformatics investigation of DNA methylation in IA, utilizing a transcriptomics-based methodology that encompassed 100 machine learning algorithms, genome-wide association studies (GWAS), Mendelian randomization (MR), and summary-data-based Mendelian randomization (SMR). Our sophisticated analytical strategy allowed for a systematic assessment of differentially methylated genes and their implications on the onset, progression, and rupture of IA. Results We identified DNA methylation-related genes (MRGs) and associated molecular pathways, and the MR and SMR analyses provided evidence for potential causal links between the observed DNA methylation events and IA predisposition. Conclusion These insights not only augment our understanding of the molecular underpinnings of IA but also underscore potential novel biomarkers and therapeutic avenues. Although our study faces inherent limitations and hurdles, it represents a groundbreaking initiative in deciphering the intricate relationship between genetic, epigenetic, and environmental factors implicated in IA pathogenesis. Graphical Keywords: Intracranial aneurysms, DNA methylation regulator, Multi-omics, Machine learning, Genome-wide association studies, Mendelian randomization