Research output: Contribution to journal › Article › peer-review
Identification of tissue-specific and common methylation quantitative trait loci in healthy individuals using MAGAR. / Scherer, Michael; Gasparoni, Gilles; Rahmouni, Souad et al.
In: Epigenetics and Chromatin, Vol. 14, No. 1, 44, 12.2021.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Identification of tissue-specific and common methylation quantitative trait loci in healthy individuals using MAGAR
AU - Scherer, Michael
AU - Gasparoni, Gilles
AU - Rahmouni, Souad
AU - Shashkova, Tatiana
AU - Arnoux, Marion
AU - Louis, Edouard
AU - Nostaeva, Arina
AU - Avalos, Diana
AU - Dermitzakis, Emmanouil T.
AU - Aulchenko, Yurii S.
AU - Lengauer, Thomas
AU - Lyons, Paul A.
AU - Georges, Michel
AU - Walter, Jörn
N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. This work was supported by the EU H2020 project SYSCID (733100), an MRC Programme Grant (MR/L019027/1) to P.A.L, and by ELIXIR Luxembourg via its data hosting service. 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”). Funding Information: We appreciate the help of Ivan Kuznetsov with data management and analysis and would like to thank Myriam Mni and the GIGA-Institute Genomics core facility for technical assistance. We appreciate the help from the data management team at the University of Luxembourg, especially from Wei Gu. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Computational biology
KW - DNA methylation
KW - Quantitative trait loci
KW - Tissue specificity
UR - http://www.scopus.com/inward/record.url?scp=85115116029&partnerID=8YFLogxK
U2 - 10.1186/s13072-021-00415-6
DO - 10.1186/s13072-021-00415-6
M3 - Article
C2 - 34530905
AN - SCOPUS:85115116029
VL - 14
JO - Epigenetics and Chromatin
JF - Epigenetics and Chromatin
SN - 1756-8935
IS - 1
M1 - 44
ER -
ID: 34257738