TY - JOUR
T1 - TreeMap
T2 - A structured approach to fine mapping of eQTL variants
AU - Liu, Li
AU - Chandrashekar, Pramod
AU - Zeng, Biao
AU - Sanderford, Maxwell D.
AU - Kumar, Sudhir
AU - Gibson, Greg
N1 - © The Author(s) 2020. Published by Oxford University Press.
PY - 2021/4/15
Y1 - 2021/4/15
N2 - 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.
AB - 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.
KW - Chromosome Mapping
KW - Colon
KW - Gene Expression
KW - Genome-Wide Association Study
KW - Hippocampus
KW - Humans
KW - Linkage Disequilibrium
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait Loci/genetics
UR - http://www.scopus.com/inward/record.url?scp=85107091268&partnerID=8YFLogxK
U2 - 10.1093/bioinformatics/btaa927
DO - 10.1093/bioinformatics/btaa927
M3 - Article
C2 - 33135051
AN - SCOPUS:85107091268
SN - 1367-4803
VL - 37
SP - 1125
EP - 1134
JO - Bioinformatics
JF - Bioinformatics
IS - 8
ER -