PlaqueQTL
PlaqueQTL builds a cell-type-resolved eQTL resource for atherosclerotic plaque entirely from public single-cell RNA-seq — no new sequencing, no genotyping array.
Core trick
Calls donor genotypes from RNA reads in public plaque single-cell data, then maps cell-type-specific cis-eQTLs without new sequencing or arrays.
Description
PlaqueQTL builds a cell-type-resolved eQTL resource for atherosclerotic plaque entirely from public single-cell RNA-seq — no new sequencing, no genotyping array. The key move: donor genotypes are called directly from the RNA reads of published plaque single-cell/single-nucleus datasets using Monopogen, recovering 3,812,318 high-quality variants across 57 donors and all 22 autosomes with zero missingness. Using these de-novo genotypes, we mapped cell-type-specific cis-eQTLs genome-wide (16,902 genes; 118,286 gene×cell-type tests) in diseased human plaque.
The method validates cleanly: across 9 cell types it recovers established GTEx artery eGenes in the expected cell type. It then does what bulk tissue cannot — it localizes the known coronary-artery-disease gene GUCY1A1 specifically to the fibroblast compartment (rs7671138, p=8.9×10⁻⁸), and it reveals a distinct class of regulation exemplified by CFDP1: a gene expressed across every cell type whose genetic effect fires only in the smooth-muscle-derived mesenchymal lineage — cell-type specificity invisible to bulk artery.
Why it matters: GWAS has found hundreds of CAD loci but rarely resolves the gene and the cell type through which a variant acts, and the standard vascular reference (GTEx) is bulk, non-diseased tissue. PlaqueQTL shows that the thousands of public single-cell datasets are themselves a latent statistical-genetics resource — every one carries recoverable genotypes — offering a low-cost, high-yield route to disease-context, cell-type-resolved regulatory maps.
README excerpt
# PlaqueQTL — Cell-Type-Resolved eQTL from De Novo Single-Cell Genotypes in Atherosclerotic Plaque ## Abstract Genome-wide association studies have identified hundreds of coronary artery disease (CAD) risk loci, but the causal variant, the gene it regulates, and the cell type in which it acts usually remain unresolved. Expression quantitative trait locus (eQTL) mapping addresses the first two, yet the principal vascular reference — GTEx — is derived from bulk, non-diseased artery, in which cell-type-specific and disease-context regulation is averaged away. We asked whether a matched genotype and single-cell resource for diseased plaque could instead be built from existing public data. Donor genotypes were called directly from the RNA reads of published single-cell/single-nucleus atherosclerosis datasets using Monopogen [1], recovering 3,812,318 high-quality variants across 57 donors and all 22 autosomes with zero missingness; these de-novo genotypes were then used to map cell-type-specific cis-eQTLs genome-wide (16,902 genes; 118,286 gene×cell-type tests) in diseased plaque. The method recovers established arterial eQTLs in the expected cell type, localizes the known CAD eGene *GUCY1A1* to fibroblasts, and reveals cell-type-specific regulation (*CFDP1*) undetectable in bulk tissue — all from reused public data, with no new sequencing. ## Significance Prior single-cell genetic analyses in atherosclerosis integrate *external* blood or immune-cell eQTLs with GWAS signals by