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- Title
Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus.
- Authors
Schulz, Herbert; Ruppert, Ann-Kathrin; Herms, Stefan; Wolf, Christiane; Mirza-Schreiber, Nazanin; Stegle, Oliver; Czamara, Darina; Forstner, Andreas J.; Sivalingam, Sugirthan; Schoch, Susanne; Moebus, Susanne; Pütz, Benno; Hillmer, Axel; Fricker, Nadine; Vatter, Hartmut; Müller-Myhsok, Bertram; Nöthen, Markus M.; Becker, Albert J.; Hoffmann, Per; Sander, Thomas
- 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 singlenucleotide 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 3Œ-mRNA transcripts of 288 genes. Hippocampal cismeQTL- 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 cisacting 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.
- Subjects
GENE expression; GENE mapping; DNA methylation; HUMAN genes; RNA methylation; BINDING sites; THETA rhythm; CELL-free DNA
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-01818-4