title: Cross-population joint analysis of eQTLs: fine mapping and functional annotation.
abstract: Mapping expression quantitative trait loci (eQTLs) has been shown as a powerful tool to uncover the genetic underpinnings of many complex traits at molecular level. In this paper, we present an integrative analysis approach that leverages eQTL data collected from multiple population groups. In particular, our approach effectively identifies multiple independent cis-eQTL signals that are consistent across populations, accounting for population heterogeneity in allele frequencies and linkage disequilibrium patterns. Furthermore, by integrating genomic annotations, our analysis framework enables high-resolution functional analysis of eQTLs. We applied our statistical approach to analyze the GEUVADIS data consisting of samples from five population groups. From this analysis, we concluded that i) jointly analysis across population groups greatly improves the power of eQTL discovery and the resolution of fine mapping of causal eQTL ii) many genes harbor multiple independent eQTLs in their cis regions iii) genetic variants that disrupt transcription factor binding are significantly enriched in eQTLs (p-value = 4.93 × 10(-22)).
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Wen
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Luca
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA; Department of Clinical and Translational Sciences, Wayne State University, Detroit, MI, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Pique-Regi
mesh_terms: D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*