Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Yang, Fan
• dc.contributor.author Wang, Jiebiao
• dc.contributor.author The GTEx Consortium
• dc.contributor.author Pierce, Brandon L.
• dc.contributor.author Chen, Lin S.
• dc.date.accessioned 2025-02-03T07:45:28Z
• dc.date.available 2025-02-03T07:45:28Z
• dc.date.issued 2017
• dc.description.abstract The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes (cis-eQTLs). More research is needed to identify effects of genetic variation on distant genes (trans-eQTLs) and understand their biological mechanisms. One common trans-eQTLs mechanism is “mediation” by a local (cis) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are “cis-mediators” of trans-eQTLs, including those “cis-hubs” involved in regulation of many trans-genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans-eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis-mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis-hubs and trans-eQTL regulation across tissue types.en
• dc.format.mimetype application/pdf
• dc.identifier.citation Yang F, Wang J; GTEx Consortium; Pierce BL, Chen LS. Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis. Genome Res. 2017 Nov;27(11):1859-71. DOI: 10.1101/gr.216754.116
• dc.identifier.doi http://dx.doi.org/10.1101/gr.216754.116
• dc.identifier.issn 1088-9051
• dc.identifier.uri http://hdl.handle.net/10230/69438
• dc.language.iso eng
• dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)
• dc.relation.ispartof Genome Research. 2017 Nov;27(11):1859-71
• dc.rights © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.other Teixits -- Anàlisica
• dc.subject.other Genòmicaca
• dc.subject.other Sistemes biològicsca
• dc.title Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysisen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion