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Nat Commun. 2017 Nov 15;8(1):1511. doi: 10.1038/s41467-017-01818-4.

Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus.

Author information

1
Cologne Center for Genomics, University of Cologne, 50931, Cologne, Germany.
2
Department of Genomics, Life & Brain Center, Institute of Human Genetics, University of Bonn, 53127, Bonn, Germany.
3
Department of Biomedicine, University of Basel, 4031, Basel, Switzerland.
4
Institute of Medical Genetics and Pathology, University Hospital Basel, 4031, Basel, Switzerland.
5
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804, Munich, Germany.
6
European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, CB10 1SD, Cambridge, UK.
7
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, 97080, Würzburg, Germany.
8
Department of Psychiatry (UPK), University of Basel, 4012, Basel, Switzerland.
9
Department of Neuropathology, University of Bonn Medical Center, 53127, Bonn, Germany.
10
Department of Epileptology, University of Bonn Medical Center, 53105, Bonn, Germany.
11
Institute of Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, 45147, Essen, Germany.
12
Genome Institute of Singapore, Singapore, 138672, Singapore.
13
TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, 55131, Mainz, Germany.
14
Department of Neurosurgery, University of Bonn Medical Center, 53127, Bonn, Germany.
15
Munich Cluster for Systems Neurology (SyNergy), 81377, Munich, Germany.
16
Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3BX, UK.
17
Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, 52425, Jülich, Germany.
18
Cologne Center for Genomics, University of Cologne, 50931, Cologne, Germany. sandert@uni-koeln.de.
19
Department of Genomics, Life & Brain Center, Institute of Human Genetics, University of Bonn, 53127, Bonn, Germany. sven.cichon@unibas.ch.
20
Department of Biomedicine, University of Basel, 4031, Basel, Switzerland. sven.cichon@unibas.ch.
21
Institute of Medical Genetics and Pathology, University Hospital Basel, 4031, Basel, Switzerland. sven.cichon@unibas.ch.
22
Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, 52425, Jülich, Germany. sven.cichon@unibas.ch.

Abstract

Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the cis-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify cis-meQTLs at 14,118 CpG methylation sites and cis-eQTLs for 302 3'-mRNA transcripts of 288 genes. Hippocampal cis-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. Cis-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of cis-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.

PMID:
29142228
PMCID:
PMC5688097
DOI:
10.1038/s41467-017-01818-4
[Indexed for MEDLINE]
Free PMC Article

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