mQTLs

mQTLs, or methylation quantitative trait loci, are genomic loci at which genetic variation is statistically associated with variation in DNA methylation at CpG dinucleotides across individuals. These associations are typically identified in population-based studies that genotype individuals and measure methylation across many CpG sites, enabling genome-wide scans for cis and trans effects.

Most studies focus on CpG methylation measured in accessible tissues using array or sequencing technologies. Common platforms include Illumina methylation arrays and whole-genome bisulfite sequencing. Associations are categorized as cis when the genetic variant lies near the CpG site (often within 1 Mb) and trans when it affects methylation at distant sites or on other chromosomes.

mQTLs can influence gene regulation by modulating methylation at promoters or enhancers, thereby affecting gene expression. They help interpret GWAS results by linking disease-associated variants to epigenetic mechanisms and potential functional consequences.

Detection uses regression models with covariates such as age, sex, estimated cell-type composition, and technical factors, along with multiple testing correction and replication in independent cohorts. Because methylation is tissue- and time-specific and influenced by environment, study design and interpretation require careful consideration of tissue type and developmental stage. Trans-meQTLs often have smaller effects and require larger samples to achieve adequate power.

Limitations include tissue specificity, dynamic methylation, and potential reverse causation in cross-sectional data. Integrating meQTL results with expression QTLs (eQTLs) and using colocalization analyses can illuminate causal pathways from genetic variation through epigenetic modification to phenotype. Public resources and databases curate meQTL findings and support cross-study comparisons.