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

[en] Background: Understanding the influence of genetic variantson 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, which fully supports identification of methQTLs from matched genotyping and DNA methylation data, and additionally the identification of quantitative 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 dataset comprising additional cell types and tissues. Finally, we validate selected methQTLs (PON1, ZNF155, NRG2) 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.

Disciplines :

Genetics & genetic processes

Author, co-author :

Scherer, Michael

Gasparoni, Gilles

Rahmouni, Souad ; Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics

Shashkova, Tatiana

Arnoux, Marion

Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie

Nostaeva, Arina

Avalos, Diana

Dermitzakis, Emmanouil T.

Aulchenko, Yurii S.

More authors (4 more)

Language :

English

Title :

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

Publication date :

2021

Journal title :

Epigenetics and Chromatin

ISSN :

1756-8935

Publisher :

BioMed Central, United Kingdom

Volume :

Issue :

Pages :

Peer reviewed :

Peer Reviewed verified by ORBi

European Projects :

H2020 - 733100 - SYSCID - A Systems medicine approach to chronic inflammatory disease

Funders :

EC - European Commission

Available on ORBi :

since 03 August 2021

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