Cargando…

TreeMap: a structured approach to fine mapping of eQTL variants

MOTIVATION: Expression quantitative trait loci (eQTL) harbor genetic variants modulating gene transcription. Fine mapping of regulatory variants at these loci is a daunting task due to the juxtaposition of causal and linked variants at a locus as well as the likelihood of interactions among multiple...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Li, Chandrashekar, Pramod, Zeng, Biao, Sanderford, Maxwell D, Kumar, Sudhir, Gibson, Greg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150140/
https://www.ncbi.nlm.nih.gov/pubmed/33135051
http://dx.doi.org/10.1093/bioinformatics/btaa927
Descripción
Sumario:MOTIVATION: Expression quantitative trait loci (eQTL) harbor genetic variants modulating gene transcription. Fine mapping of regulatory variants at these loci is a daunting task due to the juxtaposition of causal and linked variants at a locus as well as the likelihood of interactions among multiple variants. This problem is exacerbated in genes with multiple cis-acting eQTL, where superimposed effects of adjacent loci further distort the association signals. RESULTS: We developed a novel algorithm, TreeMap, that identifies putative causal variants in cis-eQTL accounting for multisite effects and genetic linkage at a locus. Guided by the hierarchical structure of linkage disequilibrium, TreeMap performs an organized search for individual and multiple causal variants. Via extensive simulations, we show that TreeMap detects co-regulating variants more accurately than current methods. Furthermore, its high computational efficiency enables genome-wide analysis of long-range eQTL. We applied TreeMap to GTEx data of brain hippocampus samples and transverse colon samples to search for eQTL in gene bodies and in 4 Mbps gene-flanking regions, discovering numerous distal eQTL. Furthermore, we found concordant distal eQTL that were present in both brain and colon samples, implying long-range regulation of gene expression. AVAILABILITY AND IMPLEMENTATION: TreeMap is available as an R package enabled for parallel processing at https://github.com/liliulab/treemap. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.