Universität zu Köln

Hass, Johanna, Walton, Esther ORCID: 0000-0002-0935-2200, Wright, Carrie ORCID: 0000-0003-1325-6067, Beyer, Andreas ORCID: 0000-0002-3891-2123, Scholz, Markus, Turner, Jessica, Liu, Jingyu ORCID: 0000-0002-1724-7523, Smolka, Michael N., Roessner, Veit, Sponheim, Scott R., Gollub, Randy L. ORCID: 0000-0002-9434-4044, Calhoun, Vince D. and Ehrlich, Stefan ORCID: 0000-0003-2132-4445 (2015). Associations between DNA methylation and schizophrenia-related intermediate phenotypes - A gene set enrichment analysis. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 59. S. 31 - 40. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD. ISSN 1878-4216

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Abstract

Multiple genetic approaches have identified microRNAs as key effectors in psychiatric disorders as they post-transcriptionally regulate expression of thousands of target genes. However, their role in specific psychiatric diseases remains poorly understood. In addition, epigenetic mechanisms such as DNA methylation, which affect the expression of both microRNAs and coding genes, are critical for our understanding of molecular mechanisms in schizophrenia. Using clinical, imaging, genetic, and epigenetic data 01 103 patients with schizophrenia and 111 healthy controls of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia, we conducted gene set enrichment analysis to identity markers for schizophrenia-associated intermediate phenotypes. Genes were ranked based on the correlation between DNA methylation patterns and each phenotype, and then searched for enrichment in 221 predicted microRNA target gene sets. We found the predicted hsa-miR-219a-5p target gene set to be significantly enriched for genes (ERIIA4, PKNOX1, ESR1, among others) whose methylation status is correlated with hippocampal volume independent of disease status Our results were strengthened by significant associations between hsa-miR-219a-5p target gene methylation patterns and hippocampus-related neuropsychological variables. IPA pathway analysis of the respective predicted hsa-miR-219a-5p target genes revealed associated network functions in behavior and developmental disorders. Altered methylation patterns of predicted hsa-miR-219a-5p target genes are associated with a structural aberration of the brain that has been proposed as a possible biomarker for schizophrenia. The (dys)regulation of microRNA target genes by epigenetic mechanisms may confer additional risk for developing psychiatric symptoms. Further study is needed to understand possible interactions between microRNAs and epigenetic changes and their impact on risk for brain-based disorders such as schizophrenia. (C) 2015 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hass, Johanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Walton, Esther UNSPECIFIED orcid.org/0000-0002-0935-2200 UNSPECIFIED Wright, Carrie UNSPECIFIED orcid.org/0000-0003-1325-6067 UNSPECIFIED Beyer, Andreas UNSPECIFIED orcid.org/0000-0002-3891-2123 UNSPECIFIED Scholz, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Turner, Jessica UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Jingyu UNSPECIFIED orcid.org/0000-0002-1724-7523 UNSPECIFIED Smolka, Michael N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Roessner, Veit UNSPECIFIED UNSPECIFIED UNSPECIFIED Sponheim, Scott R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gollub, Randy L. UNSPECIFIED orcid.org/0000-0002-9434-4044 UNSPECIFIED Calhoun, Vince D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ehrlich, Stefan UNSPECIFIED orcid.org/0000-0003-2132-4445 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-401294
DOI:	10.1016/j.pnpbp.2015.01.006
Journal or Publication Title:	Prog. Neuro-Psychopharmacol. Biol. Psychiatry
Volume:	59
Page Range:	S. 31 - 40
Date:	2015
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
Place of Publication:	OXFORD
ISSN:	1878-4216
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ESTROGEN-RECEPTOR-ALPHA; WHITE-MATTER INTEGRITY; DORSOLATERAL PREFRONTAL CORTEX; GENOME-WIDE ASSOCIATION; WORKING-MEMORY; DIFFUSION TENSOR; BRAIN STRUCTURE; AUDITORY HALLUCINATIONS; CORTICAL THICKNESS; COMMON VARIANTS Multiple languages Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40129