Identification of tissue-specific and common methylation quantitative trait loci in healthy individuals using MAGAR

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• dc.contributor.author Scherer, Michael
• dc.contributor.author Gasparoni, Gilles
• dc.contributor.author Rahmouni, Souad
• dc.contributor.author Shashkova, Tatiana
• dc.contributor.author Arnoux, Marion
• dc.contributor.author Louis, Edward J.
• dc.contributor.author Nostaeva, Arina
• dc.contributor.author Avalos, Diana
• dc.contributor.author Dermitzakis, Emmanuouil T.
• dc.contributor.author Aulchenko, Yurii S.
• dc.contributor.author Lengauer, Thomas
• dc.contributor.author Lyons, Paul A.
• dc.contributor.author Georges, Michel
• dc.contributor.author Walter, Jörn
• dc.date.accessioned 2022-04-27T10:58:02Z
• dc.date.available 2022-04-27T10:58:02Z
• dc.date.issued 2021
• dc.description.abstract Background: Understanding the influence of genetic variants on DNA methylation is fundamental for the interpretation of epigenomic data in the context of disease. There is a need for systematic approaches not only for determining methylation quantitative trait loci (methQTL), but also for discriminating general from cell type-specific effects. Results: Here, we present a two-step computational framework MAGAR ( https://bioconductor.org/packages/MAGAR ), which fully supports the identification of methQTLs from matched genotyping and DNA methylation data, and additionally allows for illuminating cell type-specific methQTL effects. In a pilot analysis, we apply MAGAR on data in four tissues (ileum, rectum, T cells, B cells) from healthy individuals and demonstrate the discrimination of common from cell type-specific methQTLs. We experimentally validate both types of methQTLs in an independent data set comprising additional cell types and tissues. Finally, we validate selected methQTLs located in the PON1, ZNF155, and NRG2 genes by ultra-deep local sequencing. In line with previous reports, we find cell type-specific methQTLs to be preferentially located in enhancer elements. Conclusions: Our analysis demonstrates that a systematic analysis of methQTLs provides important new insights on the influences of genetic variants to cell type-specific epigenomic variation.
• dc.description.sponsorship Open Access funding enabled and organized by Projekt DEAL. This work was supported by the EU H2020 project SYSCID (733100) and an MRC Programme Grant (MR/L019027/1) to P.A.L. The work of A.N. was supported by the Ministry of Education and Science of the Russian Federation via the state assignment of the Novosibirsk State University (project “Graduates 2020”)
• dc.format.mimetype application/pdf
• dc.identifier.citation Scherer M, Gasparoni G, Rahmouni S, Shashkova T, Arnoux M, Louis E et al. Identification of tissue-specific and common methylation quantitative trait loci in healthy individuals using MAGAR. Epigenetics Chromatin. 2021 Sep 16;14(1):44. DOI: 10.1186/s13072-021-00415-6
• dc.identifier.doi http://dx.doi.org/10.1186/s13072-021-00415-6
• dc.identifier.issn 1756-8935
• dc.identifier.uri http://hdl.handle.net/10230/52914
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733100
• dc.rights © Michael Scherer et al. 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Biologia computacional
• dc.subject.other Metilació de l'ADN
• dc.subject.other Epigenòmica
• dc.title Identification of tissue-specific and common methylation quantitative trait loci in healthy individuals using MAGAR
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion