IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-23243-4.html
   My bibliography  Save this article

A meta-analysis of epigenome-wide association studies in Alzheimer’s disease highlights novel differentially methylated loci across cortex

Author

Listed:
  • Rebecca G. Smith

    (University of Exeter)

  • Ehsan Pishva

    (University of Exeter
    Maastricht University)

  • Gemma Shireby

    (University of Exeter)

  • Adam R. Smith

    (University of Exeter)

  • Janou A. Y. Roubroeks

    (University of Exeter
    Maastricht University)

  • Eilis Hannon

    (University of Exeter)

  • Gregory Wheildon

    (University of Exeter)

  • Diego Mastroeni

    (Arizona State University)

  • Gilles Gasparoni

    (University of Saarland (UdS))

  • Matthias Riemenschneider

    (Saarland University Hospital (UKS))

  • Armin Giese

    (Ludwig-Maximilians-University (LMU))

  • Andrew J. Sharp

    (Icahn School of Medicine at Mount Sinai)

  • Leonard Schalkwyk

    (University of Essex)

  • Vahram Haroutunian

    (The Icahn School of Medicine at Mount Sinai
    The Icahn School of Medicine at Mount Sinai
    JJ Peters VA Medical Center)

  • Wolfgang Viechtbauer

    (Maastricht University)

  • Daniel L. A. Hove

    (Maastricht University
    University of Wuerzburg)

  • Michael Weedon

    (University of Exeter)

  • Danielle Brokaw

    (Arizona State University)

  • Paul T. Francis

    (University of Exeter)

  • Alan J. Thomas

    (Newcastle University)

  • Seth Love

    (University of Bristol)

  • Kevin Morgan

    (University of Nottingham)

  • Jörn Walter

    (University of Saarland (UdS))

  • Paul D. Coleman

    (Arizona State University)

  • David A. Bennett

    (Rush University Medical Center)

  • Philip L. Jager

    (Columbia University Medical Center
    The Broad Institute of MIT and Harvard)

  • Jonathan Mill

    (University of Exeter)

  • Katie Lunnon

    (University of Exeter)

Abstract

Epigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, although existing studies have been limited in sample size and utilized different brain regions. Here, we combine data from six DNA methylomic studies of Alzheimer’s disease (N = 1453 unique individuals) to identify differential methylation associated with Braak stage in different brain regions and across cortex. We identify 236 CpGs in the prefrontal cortex, 95 CpGs in the temporal gyrus and ten CpGs in the entorhinal cortex at Bonferroni significance, with none in the cerebellum. Our cross-cortex meta-analysis (N = 1408 donors) identifies 220 CpGs associated with neuropathology, annotated to 121 genes, of which 84 genes have not been previously reported at this significance threshold. We have replicated our findings using two further DNA methylomic datasets consisting of a further >600 unique donors. The meta-analysis summary statistics are available in our online data resource ( www.epigenomicslab.com/ad-meta-analysis/ ).

Suggested Citation

  • Rebecca G. Smith & Ehsan Pishva & Gemma Shireby & Adam R. Smith & Janou A. Y. Roubroeks & Eilis Hannon & Gregory Wheildon & Diego Mastroeni & Gilles Gasparoni & Matthias Riemenschneider & Armin Giese , 2021. "A meta-analysis of epigenome-wide association studies in Alzheimer’s disease highlights novel differentially methylated loci across cortex," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23243-4
    DOI: 10.1038/s41467-021-23243-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-23243-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-23243-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Lasse Pihlstrøm & Gemma Shireby & Hanneke Geut & Sandra Pilar Henriksen & Annemieke J. M. Rozemuller & Jon-Anders Tunold & Eilis Hannon & Paul Francis & Alan J. Thomas & Seth Love & Jonathan Mill & Wi, 2022. "Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Tiago C. Silva & Juan I. Young & Lanyu Zhang & Lissette Gomez & Michael A. Schmidt & Achintya Varma & X. Steven Chen & Eden R. Martin & Lily Wang, 2022. "Cross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Gemma Shireby & Emma L. Dempster & Stefania Policicchio & Rebecca G. Smith & Ehsan Pishva & Barry Chioza & Jonathan P. Davies & Joe Burrage & Katie Lunnon & Dorothea Seiler Vellame & Seth Love & Alan , 2022. "DNA methylation signatures of Alzheimer’s disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23243-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.