Multi-omics integrative analysis identified SNP-methylation-mRNA: Interaction in peripheral blood mononuclear cells

Area of Science:

• Genomics
• Epigenetics
• Systems Biology

Background:

• Genetic variants can impact DNA methylation, which in turn affects messenger RNA (mRNA) expression.
• Understanding these complex relationships is crucial for deciphering gene regulation and disease etiology.

Purpose of the Study:

• To comprehensively map the interplay between single nucleotide polymorphisms (SNPs), DNA methylation, and mRNA expression.
• To identify specific methylation-mediated regulatory pathways in human peripheral blood mononuclear cells (PBMCs).

Main Methods:

• Utilized in-house multi-omics data from 43 Chinese Han female subjects.
• Constructed genome-wide association trios to test SNP-methylation, methylation-mRNA, and SNP-mRNA associations.
• Employed Causal Inference Test (CIT) for identifying methylation-mediated genetic effects on mRNA.

Main Results:

• Identified 64,184 significant cis-methylation quantitative trait loci (meQTLs).
• Discovered 464 SNP-methylation-mRNA regulation chains via CIT.
• Constructed complex regulatory networks, revealing SNPs linked to specific methylation sites and multiple genes.

Conclusions:

• The findings elucidate novel methylation-mediated genetic regulation patterns.
• These insights enhance understanding of functional mechanisms in gene expression and immune/inflammatory diseases.
• The study provides a foundation for further research into genetic and epigenetic regulation of mRNA expression.