University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Florey Department of Neuroscience and Mental Health
  • Florey Department of Neuroscience and Mental Health - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Florey Department of Neuroscience and Mental Health
  • Florey Department of Neuroscience and Mental Health - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Methylome-wide association findings for major depressive disorder overlap in blood and brain and replicate in independent brain samples

    Thumbnail
    Citations
    Scopus
    Web of Science
    Altmetric
    15
    15
    Author
    Aberg, KA; Dean, B; Shabalin, AA; Chan, RF; Han, LKM; Zhao, M; van Grootheest, G; Xie, LY; Milaneschi, Y; Clark, SL; ...
    Date
    2020-06-01
    Source Title
    Molecular Psychiatry
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Dean, Brian
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Aberg, K. A., Dean, B., Shabalin, A. A., Chan, R. F., Han, L. K. M., Zhao, M., van Grootheest, G., Xie, L. Y., Milaneschi, Y., Clark, S. L., Turecki, G., Penninx, B. W. J. H. & van den Oord, E. J. C. G. (2020). Methylome-wide association findings for major depressive disorder overlap in blood and brain and replicate in independent brain samples. MOLECULAR PSYCHIATRY, 25 (6), pp.1344-1354. https://doi.org/10.1038/s41380-018-0247-6.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/253924
    DOI
    10.1038/s41380-018-0247-6
    Open Access URL
    http://europepmc.org/articles/pmc6428621?pdf=render
    Abstract
    We present the first large-scale methylome-wide association studies (MWAS) for major depressive disorder (MDD) to identify sites of potential importance for MDD etiology. Using a sequencing-based approach that provides near-complete coverage of all 28 million common CpGs in the human genome, we assay methylation in MDD cases and controls from both blood (N = 1132) and postmortem brain tissues (N = 61 samples from Brodmann Area 10, BA10). The MWAS for blood identified several loci with P ranging from 1.91 × 10-8 to 4.39 × 10-8 and a resampling approach showed that the cumulative association was significant (P = 4.03 × 10-10) with the signal coming from the top 25,000 MWAS markers. Furthermore, a permutation-based analysis showed significant overlap (P = 5.4 × 10-3) between the MWAS findings in blood and brain (BA10). This overlap was significantly enriched for a number of features including being in eQTLs in blood and the frontal cortex, CpG islands and shores, and exons. The overlapping sites were also enriched for active chromatin states in brain including genic enhancers and active transcription start sites. Furthermore, three loci located in GABBR2, RUFY3, and in an intergenic region on chromosome 2 replicated with the same direction of effect in the second brain tissue (BA25, N = 60) from the same individuals and in two independent brain collections (BA10, N = 81 and 64). GABBR2 inhibits neuronal activity through G protein-coupled second-messenger systems and RUFY3 is implicated in the establishment of neuronal polarity and axon elongation. In conclusion, we identified and replicated methylated loci associated with MDD that are involved in biological functions of likely importance to MDD etiology.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Florey Department of Neuroscience and Mental Health - Research Publications [1052]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors