eQTLHap: a tool for comprehensive eQTL analysis considering haplotypic and genotypic effects

Abstract

Abstract Motivation The high accuracy of recent haplotype phasing tools is enabling the integration of haplotype (or phase) information more widely in genetic investigations. One such possibility is phase-aware expression quantitative trait loci (eQTL) analysis, where haplotype-based analysis has the potential to detect associations that may otherwise be missed by standard SNP-based approaches. Results We present eQTLHap, a novel method to investigate associations between gene expression and genetic variants, considering their haplotypic and genotypic effect. Using multiple simulations based on real data, we demonstrate that phase-aware eQTL analysis significantly outperforms typical SNP-based methods when the causal genetic architecture involves multiple SNPs. We show that phase-aware eQTL analysis is robust to phasing errors, showing only a minor impact ($<4\%$) on sensitivity. Applying eQTLHap to real GEUVADIS and GTEx datasets detects numerous novel eQTLs undetected by a single-SNP approach, with 22 eQTLs replicating across studies or tissue types, highlighting the utility of phase-aware eQTL analysis. Availability and implementation https://github.com/ziadbkh/eQTLHap. Contact ziad.albkhetan@gmail.com Supplementary information Supplementary data are available at Briefings in Bioinformatics online.