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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; Cichon, Sven

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

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  • Media type: E-Article
  • Title: Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus
  • Contributor: 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; Cichon, Sven
  • imprint: Springer Science and Business Media LLC, 2017
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-017-01818-4
  • ISSN: 2041-1723
  • Keywords: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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 <jats:italic>cis</jats:italic>-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify <jats:italic>cis</jats:italic>-meQTLs at 14,118 CpG methylation sites and <jats:italic>cis</jats:italic>-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal <jats:italic>cis</jats:italic>-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. <jats:italic>Cis</jats:italic>-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 <jats:italic>cis</jats:italic>-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.</jats:p>
  • Access State: Open Access