Allele-Specic QTL fine-mapping with PLASMA

Abstract

We introduce PLASMA (PopuLation Allele-Specic MApping), a statistical ne- mapping method that leverages allele-specic (AS) genomic data to improve detection of quantitative trait loci (QTLs) with causal effects on molecular traits. In simulations, PLASMA accurately prioritizes causal QTL variants over a wide range of genetic architectures. Applied to RNA-Seq data from 524 kidney tumor samples, PLASMA achieves a greater power at 50 samples than conventional QTL-based ne-mapping at 500 samples: with over 17% of loci ne-mapped to within 5 causal variants compared to 2% by QTL-based ne-mapping, and a 6.9-fold overall reduction in median credible set size. PLASMA offers high accuracy even at small sample sizes, yielding a 1.3-fold reduction in median credible set size compared to QTL-based ne-mapping when applied to H3K27AC ChIP-Seq from just 28 prostate tumor/normal samples. Our results demonstrate how integrating AS activity can substantially improve the detection of causal variants from existing molecular data.