{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:01Z","timestamp":1772138041370,"version":"3.50.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01-HG008146"],"award-info":[{"award-number":["R01-HG008146"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Human Genome Research"},{"DOI":"10.13039\/100001109","name":"Flinn Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>TreeMap is available as an R package enabled for parallel processing at https:\/\/github.com\/liliulab\/treemap.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa927","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T07:22:49Z","timestamp":1603264969000},"page":"1125-1134","source":"Crossref","is-referenced-by-count":10,"title":["TreeMap: a structured approach to fine mapping of eQTL variants"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4002-7497","authenticated-orcid":false,"given":"Li","family":"Liu","sequence":"first","affiliation":[{"name":"College of Health Solutions, Arizona State University , Phoenix, AZ 85004, USA"},{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University , Tempe, AZ 85281, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0175-0423","authenticated-orcid":false,"given":"Pramod","family":"Chandrashekar","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University , Phoenix, AZ 85004, USA"},{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University , Tempe, AZ 85281, USA"}]},{"given":"Biao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, School of Biological Sciences, Georgia Institute of Technology , Atlanta, GA 30332, USA"}]},{"given":"Maxwell D","family":"Sanderford","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Evolutionary Medicine, Temple University , Philadelphia, PA 19122, USA"}]},{"given":"Sudhir","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Evolutionary Medicine, Temple University , Philadelphia, PA 19122, USA"},{"name":"Department of Biology, Temple University , Philadelphia, PA 19122, USA"},{"name":"Center for Excellence in Genome Medicine and Research, King Abdulaziz University , Jeddah 21589, Saudi Arabia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5352-5877","authenticated-orcid":false,"given":"Greg","family":"Gibson","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, School of Biological Sciences, Georgia Institute of Technology , Atlanta, GA 30332, USA"}]}],"member":"286","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"2023051612083602900_btaa927-B1","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1093\/bioinformatics\/btw018","article-title":"FINEMAP: efficient variable selection using summary data from genome-wide association studies","volume":"32","author":"Benner","year":"2016","journal-title":"Bioinformatics"},{"key":"2023051612083602900_btaa927-B2","doi-asserted-by":"crossref","first-page":"e1007607","DOI":"10.1371\/journal.pgen.1007607","article-title":"Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue","volume":"14","author":"Bhalala","year":"2018","journal-title":"PLoS Genet"},{"key":"2023051612083602900_btaa927-B3","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1038\/ng.3979","article-title":"Predicting causal variants affecting expression by using whole-genome sequencing and RNA-seq from multiple human tissues","volume":"49","author":"Brown","year":"2017","journal-title":"Nat. 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