{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T12:44:01Z","timestamp":1749041041013,"version":"3.37.3"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01GM108711","SUB-U24 CA2109993","F31CA239557"],"award-info":[{"award-number":["2R01GM108711","SUB-U24 CA2109993","F31CA239557"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Trans-acting expression quantitative trait loci (eQTLs) collectively explain a substantial proportion of expression variation, yet are challenging to detect and replicate since their effects are often individually weak. A large proportion of genetic effects on distal genes are mediated through cis-gene expression. Cis-association (between SNP and cis-gene) and gene-gene correlation conditional on SNP genotype could establish trans-association (between SNP and trans-gene). Both cis-association and gene-gene conditional correlation have effects shared across relevant tissues and conditions, and trans-associations mediated by cis-gene expression also have effects shared across relevant conditions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We proposed a Cross-Condition Mediation analysis method (CCmed) for detecting cis-mediated trans-associations with replicable effects in relevant conditions\/studies. CCmed integrates cis-association and gene-gene conditional correlation statistics from multiple tissues\/studies. Motivated by the bimodal effect-sharing patterns of eQTLs, we proposed two variations of CCmed, CCmedmost and CCmedspec for detecting cross-tissue and tissue-specific trans-associations, respectively. We analyzed data of 13 brain tissues from the Genotype-Tissue Expression (GTEx) project, and identified trios with cis-mediated trans-associations across brain tissues, many of which showed evidence of trans-association in two replication studies. We also identified trans-genes associated with schizophrenia loci in at least two brain tissues.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>CCmed software is available at http:\/\/github.com\/kjgleason\/CCmed.<\/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\/btab139","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T20:13:14Z","timestamp":1614283994000},"page":"2513-2520","source":"Crossref","is-referenced-by-count":4,"title":["CCmed: cross-condition mediation analysis for identifying replicable trans-associations mediated by cis-gene expression"],"prefix":"10.1093","volume":"37","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus , Aurora, CO 80045, USA"}]},{"given":"Kevin J.","family":"Gleason","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Chicago , Chicago, IL 60637, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3828-4400","authenticated-orcid":false,"given":"Jiebiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Pittsburgh , Pittsburgh, PA 15261, USA"}]},{"given":"Jubao","family":"Duan","sequence":"additional","affiliation":[{"name":"Unit of Functional Genomics in Psychiatry, Center for Psychiatric Genetics, NorthShore University HealthSystem , Evanston, IL 60201, USA"},{"name":"Department of Psychiatry and Behavioral Neuroscience , Chicago, IL 60637, USA"}]},{"given":"Xin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Chicago , Chicago, IL 60637, USA"}]},{"given":"Brandon L.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Chicago , Chicago, IL 60637, USA"},{"name":"Department of Human Genetics, University of Chicago , Chicago, IL 60637, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6645-5708","authenticated-orcid":false,"given":"Lin S.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Chicago , Chicago, IL 60637, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"2023051609214934500_btab139-B1","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"Aguet","year":"2020","journal-title":"Science"},{"key":"2023051609214934500_btab139-B2","doi-asserted-by":"crossref","first-page":"e1007889","DOI":"10.1371\/journal.pgen.1007889","article-title":"Integrating predicted transcriptome from multiple tissues improves association detection","volume":"15","author":"Barbeira","year":"2019","journal-title":"PLoS Genet"},{"key":"2023051609214934500_btab139-B3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1101\/gr.155192.113","article-title":"Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals","volume":"24","author":"Battle","year":"2014","journal-title":"Genome Res"},{"key":"2023051609214934500_btab139-B4","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nature24277","article-title":"Genetic effects on gene expression across human tissues","volume":"550","author":"Battle","year":"2017","journal-title":"Nature"},{"key":"2023051609214934500_btab139-B5","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/ng2109","article-title":"A genome-wide association study of global gene expression","volume":"39","author":"Dixon","year":"2007","journal-title":"Nat. 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