Cell Type-Specific Methylome-wide Association Studies Implicate Neurotrophin and Innate Immune Signaling in Major Depressive Disorder
Robin F Chan, Gustavo Turecki, Andrey A Shabalin, Jerry Guintivano, Min Zhao, Lin Y Xie, Gerard van Grootheest, Zachary A Kaminsky, Brian Dean, Brenda WJH Penninx, Karolina A Aberg, Edwin JCG van den Oord
Biological Psychiatry | ELSEVIER SCIENCE INC | Published : 2020
BACKGROUND: We sought to characterize methylation changes in brain and blood associated with major depressive disorder (MDD). As analyses of bulk tissue may obscure association signals and hamper the biological interpretation of findings, these changes were studied on a cell type-specific level. METHODS: In 3 collections of human postmortem brain (n = 206) and 1 collection of blood samples (N = 1132) of MDD cases and controls, we used epigenomic deconvolution to perform cell type-specific methylome-wide association studies within subpopulations of neurons/glia for the brain data and granulocytes/T cells/B cells/monocytes for the blood data. Sorted neurons/glia from a fourth postmortem brain ..View full abstract
Awarded by National Institute of Mental Health
Awarded by Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw)
This project was supported by the National Institute of Mental Health (Grant No. R01MH099110 [to EJCGvdO]). Postmortem brain tissues were received from the Victorian Brain Bank, which is supported by the Florey Institute of Neuroscience and Mental Health and the Alfred and Victorian Forensic Institute of Medicine and funded by Australia's National Health and Medical Research Council and Parkinson's Victoria; the Stanley Medical Research Institute; the Netherlands Brain Bank, Netherlands Institute of Neuroscience, Amsterdam; the Harvard Brain Tissue Resource Center; and the Douglas-Bell Canada Brain Bank, Douglas Institute Research Center, Canada. The infrastructure for the NESDA study is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw) (Grant No. 10-000-1002) and via financial contributions from participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, and Rob Giel Onderzoekcentrum).BP has received research funding (nonrelated) from Jansen Research and Boehringer Ingelheim. All other authors report no biomedical financial interests or potential conflicts of interest.