eQTLMAPT

eQTLMAPT performs expression quantitative trait locus (eQTL) mediation analysis to identify mediation effects where trans-eQTLs influence remote gene expression via local transcripts and to estimate significance using permutation testing and generalized Pareto distribution modeling.

Key Features:

• R package: Implemented as an R package for eQTL mediation analysis workflows.
• Efficient Permutation Testing: Incorporates permutation procedures to control for multiple testing in large-scale genomic analyses.
• Adaptive Permutation Scheme: Employs an adaptive permutation scheme that opportunistically prunes permutations to reduce computational overhead.
• Generalized Pareto Distribution (GPD): Models the null distribution with a generalized Pareto distribution trained from a limited number of permutations to estimate significance levels.
• Integration with confounding adjustment: Supports combining permutation schemes with methods for confounding adjustment in mediation analyses.
• Performance: Demonstrated increased resolution of estimated significance and substantial speed improvements relative to existing methods.

Scientific Applications:

• Interpretation of GWAS loci: Supports interpretation of disease-associated variants identified through genome-wide association studies by assessing mediated regulatory effects.
• Trans-eQTL mediation discovery: Identifies cases where trans-eQTLs affect remote gene expression via local transcripts.
• Regulatory mechanism elucidation: Aids in uncovering indirect effects of genetic variation on gene expression to inform biological pathways underlying complex traits and diseases.

Methodology:

Adaptive permutation procedures with opportunistic pruning for permutation-based multiple testing control, null-distribution modeling using a generalized Pareto distribution trained from limited permutations, and integration of permutation schemes with confounding-adjustment methods for mediation analysis of trans-eQTLs via local transcripts.