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

Author

Listed:
  • Herbert Schulz

    (University of Cologne)

  • Ann-Kathrin Ruppert

    (University of Cologne)

  • Stefan Herms

    (University of Bonn
    University of Basel
    University Hospital Basel)

  • Christiane Wolf

    (Max Planck Institute of Psychiatry
    European Molecular Biology Laboratory, European Bioinformatics Institute
    University of Würzburg)

  • Nazanin Mirza-Schreiber

    (Max Planck Institute of Psychiatry)

  • Oliver Stegle

    (European Molecular Biology Laboratory, European Bioinformatics Institute)

  • Darina Czamara

    (Max Planck Institute of Psychiatry)

  • Andreas J. Forstner

    (University of Bonn
    University of Basel
    University of Basel)

  • Sugirthan Sivalingam

    (University of Bonn)

  • Susanne Schoch

    (University of Bonn Medical Center
    University of Bonn Medical Center)

  • Susanne Moebus

    (University Duisburg-Essen)

  • Benno Pütz

    (Max Planck Institute of Psychiatry)

  • Axel Hillmer

    (Genome Institute of Singapore
    TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH)

  • Nadine Fricker

    (University of Bonn)

  • Hartmut Vatter

    (University of Bonn Medical Center)

  • Bertram Müller-Myhsok

    (Max Planck Institute of Psychiatry
    Munich Cluster for Systems Neurology (SyNergy)
    University of Liverpool)

  • Markus M. Nöthen

    (University of Bonn)

  • Albert J. Becker

    (University of Bonn Medical Center)

  • Per Hoffmann

    (University of Bonn
    University of Basel
    University Hospital Basel
    Institute of Neuroscience and Medicine (INM-1), Research Center Jülich)

  • Thomas Sander

    (University of Cologne)

  • Sven Cichon

    (University of Bonn
    University of Basel
    University Hospital Basel
    Institute of Neuroscience and Medicine (INM-1), Research Center Jülich)

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.

Suggested Citation

  • Herbert Schulz & Ann-Kathrin Ruppert & Stefan Herms & Christiane Wolf & Nazanin Mirza-Schreiber & Oliver Stegle & Darina Czamara & Andreas J. Forstner & Sugirthan Sivalingam & Susanne Schoch & Susanne, 2017. "Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01818-4
    DOI: 10.1038/s41467-017-01818-4
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