TreeMap: a structured approach to fine mapping of eQTL variants.
Bioinformatics
; 37(8): 1125-1134, 2021 05 23.
Article
en En
| MEDLINE
| ID: mdl-33135051
ABSTRACT
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.
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Banco de datos:
MEDLINE
Asunto principal:
Sitios de Carácter Cuantitativo
/
Estudio de Asociación del Genoma Completo
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article