Association of CNVs with methylation variation

Area of Science:

• Genetics
• Epigenetics
• Genomics

Background:

• Germline copy number variants (CNVs) and single-nucleotide polymorphisms (SNPs) contribute to genetic variation.
• The phenotypic effects of SNPs are well-studied, but CNV effects are less understood.

Purpose of the Study:

• To investigate the association between germline CNVs and CpG methylation genome-wide.
• To understand how CNVs affect cellular phenotype through epigenetic modifications.

Main Methods:

• Utilized paired CNV and methylation data from the 1000 Genomes and HapMap projects.
• Performed genome-wide methylation quantitative trait locus (mQTL) analysis to identify CNV-CpG associations.

Main Results:

• Identified associations between individual CNVs and methylation of multiple CpGs, and vice versa.
• Found that CNV-associated methylation changes correlate with gene expression.
• CNV-mQTLs were enriched in regulatory regions, transcription factor-binding sites (TFBSs), and involved in long-range interactions.
• Observed CNV-mQTL associations with imprinted genes and genes previously identified by genome-wide association studies (GWASs).

Conclusions:

• Germline CNVs are associated with CpG methylation patterns across the genome.
• Structural variation and DNA methylation together may influence cellular phenotype.