QRank

QRank applies a Quantile Rank-score based test to identify expression quantitative trait loci (eQTLs) associated with conditional quantiles of gene expression, enabling detection of genetic effects beyond mean shifts.

Key Features:

• Quantile Rank-score Based Test: QRank employs a Quantile Rank-score based test (QRank) that models conditional quantile functions of gene expression to detect associations beyond mean effects.
• Detection of higher-order associations: The method identifies variance eQTLs and eQTLs affecting specific quantiles of expression that are often missed by traditional linear regression.
• Complementary analysis on GTEx: Application to Genotype-Tissue Expression (GTEx) project data reveals eQTLs with heterogeneous effects across quantile levels, complementing existing methodologies.
• Enrichment in GWAS SNPs: eQTLs identified by QRank show greater enrichment in genome-wide significant single nucleotide polymorphisms (SNPs) from the GWAS catalog.
• Tissue specificity: eQTLs detected by QRank tend to be more tissue-specific compared to those identified by linear regression.

Scientific Applications:

• Understanding molecular mechanisms: Identifying quantile-specific and variance-associated eQTLs aids interpretation of genetic regulation underlying complex traits.
• Therapeutic development: Quantile-resolved eQTLs can inform prioritization of genetic variants and mechanisms for therapeutic research.
• Tissue-specific insights: Detection of tissue-specific eQTLs supports studies of tissue-specific gene regulation in health and disease.

Methodology:

Application of a Quantile Rank-score based test modeling conditional quantile functions of gene expression; detection of variance and quantile-specific eQTLs; comparative analysis against linear regression; application to GTEx data; enrichment testing against the GWAS catalog and assessment of tissue-specificity.