Journal Article

FZJ-2017-08327

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus.

Schulz, H. ; Ruppert, A.-K. ; Herms, S. ; Wolf, C. ; Mirza-Schreiber, N. ; Stegle, O. ; Czamara, D. ; Forstner, A. J. ; Sivalingam, S. ; Schoch, S. ; Moebus, S. ; Pütz, B. ; Hillmer, A. ; Fricker, N. ; Vatter, H. ; Müller-Myhsok, B. ; Nöthen, M. M. ; Becker, A. J. ; Hoffmann, P. ; Sander, T. (Corresponding author) ; Cichon, S. (Corresponding author)FZJ*

2017
Nature Publishing Group London

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Please use a persistent id in citations: http://hdl.handle.net/2128/16211  doi:10.1038/s41467-017-01818-4

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.

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Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)

Research Program(s):

1. 571 - Connectivity and Activity (POF3-571) (POF3-571)

Appears in the scientific report 2017

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