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

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; Noethen, Markus M.; Becker, Albert J.; Hoffmann, Per; Sander, Thomas; Cichon, Sven

doi:10.1038/s41467-017-01818-4

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

MPG-Autoren

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Wolf, Christiane
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;
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Mirza-Schreiber, Nazanin
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Czamara, Darina
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Pütz, Benno
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Müller-Myhsok, Bertram
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;
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Zitation

Schulz, H., Ruppert, A.-K., Herms, S., Wolf, C., Mirza-Schreiber, N., Stegle, O., et al. (2017). Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus. NATURE COMMUNICATIONS, 8: 1511. doi:10.1038/s41467-017-01818-4.

Zitierlink: https://hdl.handle.net/21.11116/0000-0001-9F4A-A

Zusammenfassung

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.