Journal Article

DNA methylation modulated genetic variant effect on gene transcriptional regulation

Jain, Rahi, Zeng, Yong, He, Housheng Hansen, Lam, Magnus, Wei, Gong-Hong, Zhong, Yuan, Xu, Wei, Guo, Haiyang, Xu, Wenjie, Ahmed, Musaddeque

2023

Overview

Background Expression quantitative trait locus (eQTL) analysis has emerged as an important tool in elucidating the link between genetic variants and gene expression, thereby bridging the gap between risk SNPs and associated diseases. We recently identified and validated a specific case where the methylation of a CpG site influences the relationship between the genetic variant and gene expression. Results Here, to systematically evaluate this regulatory mechanism, we develop an extended eQTL mapping method, termed DNA methylation modulated eQTL (memo-eQTL). Applying this memo-eQTL mapping method to 128 normal prostate samples enables identification of 1063 memo-eQTLs, the majority of which are not recognized as conventional eQTLs in the same cohort. We observe that the methylation of the memo-eQTL CpG sites can either enhance or insulate the interaction between SNP and gene expression by altering CTCF-based chromatin 3D structure. Conclusions This study demonstrates the prevalence of memo-eQTLs paving the way to identify novel causal genes for traits or diseases associated with genetic variations.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Animal Genetics and Genomics / Binding sites / Bioinformatics / Biomedical and Life Sciences / Chromatin / Chromatin 3D structure / Chromosome Mapping / CpG islands / CTCF / DNA Methylation / eQTL / Evolutionary Biology / Gene expression / Gene Expression Regulation / Gene mapping / Gene regulation / genes / Genetic diversity / Genome-Wide Association Study - methods / Genomes / Human Genetics / Humans / Life Sciences / Male / meCpG / Memo-eQTL / Methods / Microbial Genetics and Genomics / Plant Genetics and Genomics / Polymorphism, Single Nucleotide / Prostate cancer / Quantitative Trait Loci / risk / Single-nucleotide polymorphism / SNP / transcription (genetics)