Pleiotropic Effects of Trait-Associated Genetic Variation on DNA Methylation: Utility for Refining GWAS Loci.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620432
Title:
Pleiotropic Effects of Trait-Associated Genetic Variation on DNA Methylation: Utility for Refining GWAS Loci.
Authors:
Hannon, E.; Weedon, M.; Bray, N.; O'Donovan, M.; Mill, Jonathan
Abstract:
Most genetic variants identified in genome-wide association studies (GWASs) of complex traits are thought to act by affecting gene regulation rather than directly altering the protein product. As a consequence, the actual genes involved in disease are not necessarily the most proximal to the associated variants. By integrating data from GWAS analyses with those from genetic studies of regulatory variation, it is possible to identify variants pleiotropically associated with both a complex trait and measures of gene regulation. In this study, we used summary-data-based Mendelian randomization (SMR), a method developed to identify variants pleiotropically associated with both complex traits and gene expression, to identify variants associated with complex traits and DNA methylation. We used large DNA methylation quantitative trait locus (mQTL) datasets generated from two different tissues (blood and fetal brain) to prioritize genes for >40 complex traits with robust GWAS data and found considerable overlap with the results of SMR analyses performed with expression QTL (eQTL) data. We identified multiple examples of variable DNA methylation associated with GWAS variants for a range of complex traits, demonstrating the utility of this approach for refining genetic association signals.
Citation:
Pleiotropic Effects of Trait-Associated Genetic Variation on DNA Methylation: Utility for Refining GWAS Loci. 2017, 100 (6):954-959 Am. J. Hum. Genet.
Publisher:
Cell Press
Journal:
American journal of human genetics
Issue Date:
1-Jun-2017
URI:
http://hdl.handle.net/11287/620432
DOI:
10.1016/j.ajhg.2017.04.013
PubMed ID:
28528868
Additional Links:
https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(17)30158-1
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
1537-6605
Appears in Collections:
Honorary contracts publications; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHannon, E.en
dc.contributor.authorWeedon, M.en
dc.contributor.authorBray, N.en
dc.contributor.authorO'Donovan, M.en
dc.contributor.authorMill, Jonathanen
dc.date.accessioned2017-10-11T14:52:27Z-
dc.date.available2017-10-11T14:52:27Z-
dc.date.issued2017-06-01-
dc.identifier.citationPleiotropic Effects of Trait-Associated Genetic Variation on DNA Methylation: Utility for Refining GWAS Loci. 2017, 100 (6):954-959 Am. J. Hum. Genet.en
dc.identifier.issn1537-6605-
dc.identifier.pmid28528868-
dc.identifier.doi10.1016/j.ajhg.2017.04.013-
dc.identifier.urihttp://hdl.handle.net/11287/620432-
dc.description.abstractMost genetic variants identified in genome-wide association studies (GWASs) of complex traits are thought to act by affecting gene regulation rather than directly altering the protein product. As a consequence, the actual genes involved in disease are not necessarily the most proximal to the associated variants. By integrating data from GWAS analyses with those from genetic studies of regulatory variation, it is possible to identify variants pleiotropically associated with both a complex trait and measures of gene regulation. In this study, we used summary-data-based Mendelian randomization (SMR), a method developed to identify variants pleiotropically associated with both complex traits and gene expression, to identify variants associated with complex traits and DNA methylation. We used large DNA methylation quantitative trait locus (mQTL) datasets generated from two different tissues (blood and fetal brain) to prioritize genes for >40 complex traits with robust GWAS data and found considerable overlap with the results of SMR analyses performed with expression QTL (eQTL) data. We identified multiple examples of variable DNA methylation associated with GWAS variants for a range of complex traits, demonstrating the utility of this approach for refining genetic association signals.en
dc.language.isoenen
dc.publisherCell Pressen
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S0002-9297(17)30158-1en
dc.rightsArchived with thanks to American journal of human geneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors-
dc.subject.meshBrain-
dc.subject.meshCrohn Disease-
dc.subject.meshDNA Methylation-
dc.subject.meshFetus-
dc.subject.meshGenetic Pleiotropy-
dc.subject.meshGenetic Variation-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHumans-
dc.subject.meshMendelian Randomization Analysis-
dc.subject.meshMigraine Disorders-
dc.subject.meshQuantitative Trait Loci-
dc.subject.meshQuantitative Trait, Heritable-
dc.subject.meshRepressor Proteins-
dc.titlePleiotropic Effects of Trait-Associated Genetic Variation on DNA Methylation: Utility for Refining GWAS Loci.en
dc.typeJournal Articleen
dc.identifier.journalAmerican journal of human geneticsen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionPublisheden

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