Role of DNA methylation in the relationship between glioma risk factors and glioma incidence: a two-step Mendelian randomization study

Autor: Amy E. Howell, Caroline Relton, Richard M. Martin, Jie Zheng, Kathreena M. Kurian
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-15 (2023)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-023-33621-1
Popis: Abstract Genetic evidence suggests glioma risk is altered by leukocyte telomere length, allergic disease (asthma, hay fever or eczema), alcohol consumption, childhood obesity, low-density lipoprotein cholesterol (LDLc) and triglyceride levels. DNA methylation (DNAm) variation influences many of these glioma-related traits and is an established feature of glioma. Yet the causal relationship between DNAm variation with both glioma incidence and glioma risk factors is unknown. We applied a two-step Mendelian randomization (MR) approach and several sensitivity analyses (including colocalization and Steiger filtering) to assess the association of DNAm with glioma risk factors and glioma incidence. We used data from a recently published catalogue of germline genetic variants robustly associated with DNAm variation in blood (32,851 participants) and data from a genome-wide association study of glioma risk (12,488 cases and 18,169 controls, sub-divided into 6191 glioblastoma cases and 6305 non-glioblastoma cases). MR evidence indicated that DNAm at 3 CpG sites (cg01561092, cg05926943, cg01584448) in one genomic region (HEATR3) had a putative association with glioma and glioblastoma risk (False discovery rate [FDR]
Databáze: Directory of Open Access Journals
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