TY  - JOUR
AU  - Shen, Xueyi
AU  - Barbu, Miruna
AU  - Caramaschi, Doretta
AU  - Arathimos, Ryan
AU  - Czamara, Darina
AU  - David, Friederike S
AU  - Dearman, Anna
AU  - Dilkes, Evelyn
AU  - Herrera-Rivero, Marisol
AU  - Huider, Floris
AU  - Kühn, Luise
AU  - Lu, Kuan-Chen
AU  - Palviainen, Teemu
AU  - Schowe, Alicia M
AU  - Shireby, Gemma
AU  - Weihs, Antoine
AU  - Wong, Chloe C Y
AU  - Davyson, Eleanor
AU  - Casey, Hannah
AU  - Adams, Mark J
AU  - Allgaier, Antje-Kathrin
AU  - Barber, Michael
AU  - Burrage, Joe
AU  - Caspi, Avshalom
AU  - Costeira, Ricardo
AU  - Dunn, Erin C
AU  - Feldmann, Lisa
AU  - Frank, Josef
AU  - Freisleder, Franz J
AU  - Gadd, Danni A
AU  - Greimel, Ellen
AU  - Hannon, Eilis
AU  - Harris, Sarah E
AU  - Homuth, Georg
AU  - Howard, David M
AU  - Iurato, Stella
AU  - Korhonen, Tellervo
AU  - Lu, Tzu-Pin
AU  - Martin, Nicholas G
AU  - Martins, Jade
AU  - McDermott, Edel
AU  - Meinert, Susanne
AU  - Navarro, Pau
AU  - Ollikainen, Miina
AU  - Pehl, Verena
AU  - Piechaczek, Charlotte
AU  - Scherff, Aline D
AU  - Stein, Frederike
AU  - Streit, Fabian
AU  - Teumer, Alexander
AU  - Völzke, Henry
AU  - van Dongen, Jenny
AU  - Walker, Rosie M
AU  - Yusupov, Natan
AU  - Arseneault, Louise
AU  - Bell, Jordana T
AU  - Berger, Klaus
AU  - Binder, Elisabeth
AU  - Boomsma, Dorret I
AU  - Cox, Simon R
AU  - Dannlowski, Udo
AU  - Evans, Kathryn L
AU  - Fisher, Helen L
AU  - Forstner, Andreas J
AU  - Grabe, Hans J
AU  - Kaprio, Jaakko
AU  - Kircher, Tilo
AU  - Kopf-Beck, Johannes
AU  - Kumari, Meena
AU  - Kuo, Po-Hsiu
AU  - Li, Qingqin S
AU  - Moffitt, Terrie E
AU  - Mulcahy, Hugh
AU  - Murphy, Therese M
AU  - Schulte-Körne, Gerd
AU  - Mill, Jonathan
AU  - Lewis, Cathryn M
AU  - Wray, Naomi R
AU  - McIntosh, Andrew M
TI  - A methylome-wide association study of major depression with out-of-sample case-control classification and trans-ancestry comparison.
JO  - Nature Mental Health
VL  - 3
IS  - 10
SN  - 2731-6076
CY  - London
PB  - Nature Publishing Group UK
M1  - DZNE-2025-01165
SP  - 1152 - 1167
PY  - 2025
AB  - Major depression (MD) is a leading cause of global disease burden, and both experimental and population-based studies suggest that differences in DNA methylation may be associated with the condition. However, previous DNA methylation studies have, so far, not been widely replicated, suggesting a need for larger meta-analysis studies. Here we conducted a meta-analysis of methylome-wide association analysis for lifetime MD across 18 studies of 24,754 European-ancestry participants (5,443 MD cases) and an East Asian sample (243 cases, 1,846 controls). We identified 15 CpG sites associated with lifetime MD with methylome-wide significance. The methylation score created using the methylome-wide association analysis summary statistics was significantly associated with MD status in an out-of-sample classification analysis (area under the curve 0.53). Methylation score was also associated with five inflammatory markers, with the strongest association found with tumor necrosis factor beta. Mendelian randomization analysis revealed 23 CpG sites potentially causally linked to MD, with 7 replicated in an independent dataset. Our study provides evidence that variations in DNA methylation are associated with MD, and further evidence supporting involvement of the immune system.
KW  - DNA methylation (Other)
KW  - Depression (Other)
KW  - Epigenomics (Other)
KW  - Predictive markers (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41069367
C2  - pmc:PMC12504109
DO  - DOI:10.1038/s44220-025-00486-4
UR  - https://pub.dzne.de/record/281647
ER  -