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Exhaustive search for epistatic effects on the human methylome

Egli, Tobias and Vukojevic, Vanja and Sengstag, Thierry and Jacquot, Martin and Cabezón, Rubén and Coynel, David and Freytag, Virginie and Heck, Angela and Vogler, Christian and de Quervain, Dominique J.-F. and Papassotiropoulos, Andreas and Milnik, Annette. (2017) Exhaustive search for epistatic effects on the human methylome. Scientific Reports, 7 (1). p. 13669.

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Abstract

Studies assessing the existence and magnitude of epistatic effects on complex human traits provide inconclusive results. The study of such effects is complicated by considerable increase in computational burden, model complexity, and model uncertainty, which in concert decrease model stability. An additional source introducing significant uncertainty with regard to the detection of robust epistasis is the biological distance between the genetic variation and the trait under study. Here we studied CpG methylation, a genetically complex molecular trait that is particularly close to genomic variation, and performed an exhaustive search for two-locus epistatic effects on the CpG-methylation signal in two cohorts of healthy young subjects. We detected robust epistatic effects for a small number of CpGs (N = 404). Our results indicate that epistatic effects explain only a minor part of variation in DNA-CpG methylation. Interestingly, these CpGs were more likely to be associated with gene-expression of nearby genes, as also shown by their overrepresentation in DNase I hypersensitivity sites and underrepresentation in CpG islands. Finally, gene ontology analysis showed a significant enrichment of these CpGs in pathways related to HPV-infection and cancer.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Psychology (Papassotiropoulos)
UniBasel Contributors:Papassotiropoulos, Andreas
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2045-2322
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:10 Sep 2018 17:17
Deposited On:16 May 2018 07:01

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