meQTL

MeQTL stands for methylation quantitative trait locus, a genetic locus at which variation in genotype is associated with variation in DNA methylation at a CpG site or region. MeQTLs are typically categorized as cis-meQTLs when the single-nucleotide polymorphism and the methylation site lie nearby (commonly within 1 megabase) and trans-meQTLs when the association occurs between distant loci, potentially on different chromosomes.

Methods: Studies combine genotype data with DNA methylation measurements from individuals, often using array-based platforms or sequencing. Methylation values are analyzed as beta values or logit-transformed M-values. Association testing is performed with linear models (or mixed models), adjusting for covariates such as age, sex, batch effects, ancestry, and estimated cell-type composition. Because millions of SNP–CpG pairs are tested, stringent multiple-testing correction is used, generating cis- and trans-meQTL maps.

Biological interpretation and resources: MeQTLs reveal genetic influences on the epigenome and can help link genetic variation to gene regulation and disease risk. Colocalization analyses with GWAS and integration with eQTL data can identify candidate causal variants and regulatory mechanisms. Public resources such as the BIOS QTL Browser and ARIES provide searchable meQTL catalogs, while cross-tissue maps enable exploration of tissue specificity.

Limitations and considerations: Methylation is highly tissue- and cell-type specific, so analyses must account for cellular heterogeneity. Causality is challenging to infer from association studies; methylation can be a cause, consequence, or mediator of transcriptional changes. Sample size, technical variation, and data processing choices influence meQTL discovery. Future work increasingly combines meQTL with other QTL types and single-cell methylation data to resolve context-specific regulatory effects.