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Genetic estimators of DNA methylation provide insights into the molecular basis of polygenic traits

Freytag, Virginie and Vukojevic, Vanja and Wagner-Thelen, Holger and Milnik, Annette and Vogler, Christian and Leber, Markus and Weinhold, Leonie and Böhmer, Anne C. and Riedel-Heller, Steffi and Maier, Wolfgang and de Quervain, Dominique J.-F. and Ramirez, Alfredo and Papassotiropoulos, Andreas. (2018) Genetic estimators of DNA methylation provide insights into the molecular basis of polygenic traits. Translational Psychiatry, 8 (31). pp. 1-13.

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Official URL: https://edoc.unibas.ch/66834/

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Abstract

The large biological distance between genetic risk loci and their mechanistic consequences in the tissue of interest limits the ability to establish functionality of susceptibility variants for genetically complex traits. Such a biological gap may be reduced through the systematic study of molecular mediators of genomic action, such as epigenetic modification. Here, we report the identification of robust genetic estimators of whole-blood CpG methylation, which can serve as intermediate molecular traits amenable to association testing with other genetically complex traits. We describe the relationship between these estimators and gene expression, demonstrate their genome-wide applicability to association testing even in the absence of individual genotypic data, and show that these estimators powerfully identify methylation-related genomic loci associated with polygenic traits and common diseases, such as schizophrenia. The use of genetic estimators for blood DNA methylation, which are made publically available, can serve as a valuable tool for the identification of epigenetic underpinnings of complex traits.
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:2158-3188
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:18 Feb 2019 10:51
Deposited On:05 Dec 2018 16:55

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