Genetic impacts on DNA methylation help elucidate regulatory genomic processes.

Area of Science:

• Genomics
• Epigenetics
• Human genetics

Background:

• Understanding genetic influences on DNA methylation is crucial for elucidating gene regulation and disease etiology.
• Genetic variations play a significant role in modulating DNA methylation patterns.

Purpose of the Study:

• To conduct a comprehensive methylation quantitative trait loci (meQTL) analysis using the Illumina Infinium MethylationEPIC array.
• To investigate the overlap between genetic effects on DNA methylation and various human traits, including diseases.

Main Methods:

• Analysis of DNA methylation data from 2358 blood samples across three UK cohorts using the Illumina Infinium MethylationEPIC array.
• Performed heritability and meQTL analyses across 724,499 CpG sites.
• Conducted co-localisation analyses between meQTLs and 56 human traits, alongside enrichment analyses with expression quantitative trait loci (eQTLs).

Main Results:

• Identified that single nucleotide polymorphisms (SNPs) affect methylation levels at 34.2% of CpG sites, with 98% being cis-acting.
• Discovered 1520 co-localisations between meQTLs and 34 human phenotypes, including associations with genes linked to total cholesterol and inflammatory bowel disease.
• Revealed mechanisms for cis- and trans-meQTLs, such as disruption of transcription factor binding sites and regulation of distal DNA methylation.

Conclusions:

• The findings enhance the understanding of DNA methylation variability mechanisms.
• Results provide valuable information for prioritizing genome-wide association study (GWAS) variants for functional studies.
• A database and viewer for MeQTL EPIC data are publicly available online.