Journal article

Cell-type-specific methylome-wide association studies implicate neurodegenerative processes and neuroimmune communication in major depressive disorder

Robin Chan, Gustavo Turecki, Andrey Shabalin, Jerry Guintivano, Min Zhao, Lin Xie, Gerard van Grootheest, Zachary Kaminsky, Brian Dean, Brenda WJH Penninx, Karolina Aberg, Edwin JCG van den Oord

Published : 2018


We studied the methylome in three collections of human postmortem brain (N=206) and blood samples (N=1,132) of subjects with major depressive disorder (MDD) and controls. Using an epigenomic deconvolution approach we performed cell-type-specific methylome-wide association studies (MWAS) within sub-populations of neurons/glia and granulocytes/T-cells/B-cells/monocytes for bulk brain and blood data, respectively. Multiple MWAS findings in neurons/glia replicated across brain collections (ORs=509-538, P-values<1×10 −5 ) and were reproducible in an array-based MWAS of sorted neurons/glia from a fourth brain collection (N=58). Pathway analyses implicated p75 NTR /VEGF signaling, neurodegeneration..

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