CiseQTLs

Cis-eQTLs are genetic variants that influence the expression level of nearby genes, typically within a megabase. They are distinguished from trans-eQTLs, which affect distant genes or genes on different chromosomes. Cis-eQTL effects are often tissue- and context-specific, reflecting local regulatory mechanisms such as promoters, enhancers, or splice regulation.

Detection involves integrating genotype data with gene expression measurements from the same individuals, usually in a single tissue. For each gene, variants within a defined cis window are tested for association with expression using linear regression or linear mixed models, with genotype dosage as the predictor and expression level as the outcome. Covariates such as ancestry principal components, sex, age, and technical factors are included, and multiple-testing is controlled with false discovery rate or permutation-based methods.

Common cis-window choices range from 250 kilobases to 1 megabase around the transcription start site, though there is no universal standard. Lead cis-eQTLs are reported with effect sizes and direction, and results are often integrated across cohorts to improve power.

Applications include annotating GWAS loci by identifying potential regulatory genes and performing colocalization analyses to assess whether the same variant influences expression and a trait. Fine-mapping and integrative approaches help pinpoint likely causal regulatory variants.

Limitations include dependence on sample size and tissue availability, sensitivity to linkage disequilibrium, and potential confounding by technical or biological factors. Findings may not generalize across populations or conditions, and replication is important.