Methylome-wide association findings for major depressive disorder overlap in blood and brain and replicate in independent brain samples
Karolina A Aberg, Brian Dean, Andrey A Shabalin, Robin F Chan, Laura KM Han, Min Zhao, Gerard van Grootheest, Lin Y Xie, Yuri Milaneschi, Shaunna L Clark, Gustavo Turecki, Brenda WJH Penninx, Edwin JCG van den Oord
Molecular Psychiatry | NATURE PUBLISHING GROUP | Published : 2020
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..View full abstract
Awarded by National Institute of Mental Health
Awarded by Netherlands Organization for Scientific Research (Geestkracht program grant)
Awarded by National Institutes of Health (NIH)
The current methylation study was supported by grant R01MH099110 from the National Institute of Mental Health. Tissues were received from five brain banks, including the Victorian Brain Bank, supported by The Florey Institute of Neuroscience and Mental Health, The Alfred and Victorian Forensic Institute of Medicine and funded by Australia's National Health & 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. Funding for NESDA was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10-000-1002); the Center for Medical Systems Biology (CSMB, NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University's Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, R01D0042157-01A, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO.