Universität zu Köln

Freytag, Virginie, Vukojevic, Vanja, Wagner-Thelen, Holger, Milnik, Annette ORCID: 0000-0002-3933-3289, Vogler, Christian, Leber, Markus, Weinhold, Leonie, Boehmer, Anne C., Riedel-Heller, Steffi, Maier, Wolfgang, de Quervain, Dominique J. -F., Ramirez, Alfredo ORCID: 0000-0003-4991-763X and Papassotiropoulos, Andreas ORCID: 0000-0002-2210-9651 (2018). Genetic estimators of DNA methylation provide insights into the molecular basis of polygenic traits. Transl. Psychiatr., 8. NEW YORK: NATURE PUBLISHING GROUP. ISSN 2158-3188

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Freytag, Virginie UNSPECIFIED UNSPECIFIED UNSPECIFIED Vukojevic, Vanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner-Thelen, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Milnik, Annette UNSPECIFIED orcid.org/0000-0002-3933-3289 UNSPECIFIED Vogler, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Leber, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Weinhold, Leonie UNSPECIFIED UNSPECIFIED UNSPECIFIED Boehmer, Anne C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riedel-Heller, Steffi UNSPECIFIED UNSPECIFIED UNSPECIFIED Maier, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED de Quervain, Dominique J. -F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramirez, Alfredo UNSPECIFIED orcid.org/0000-0003-4991-763X UNSPECIFIED Papassotiropoulos, Andreas UNSPECIFIED orcid.org/0000-0002-2210-9651 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-198407
DOI:	10.1038/s41398-017-0070-x
Journal or Publication Title:	Transl. Psychiatr.
Volume:	8
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	2158-3188
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SUSCEPTIBILITY LOCI; EXPRESSION; SCHIZOPHRENIA; ASSOCIATION; GENOTYPE; DISEASE; REGULARIZATION; TRANSCRIPTION; DEMENTIA; CORTEX Multiple languages Psychiatry Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19840