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Bartels, M.* ; van de Weijer, M.P.* ; Azcona-Granada, N.* ; Baselmans, B.M.L.* ; Suderman, M.* ; Soerensen, M.* ; Buchwald, J.* ; Mulder, R.H.* ; Rawal, R.* ; Luciano, M.* ; Bonder, M.J.* ; Choudhary, P.* ; Lowry, E.* ; Lind, P.A.* ; Schwartz, J.* ; Debrabant, B.* ; Ollikainen, M.* ; Felix, J.F.* ; Bakermans-Kranenburg, M.J.* ; Tiemeier, H.* ; Gieger, C. ; Waldenberger, M. ; Martin, N.G.* ; Vokonas, P.* ; Baccarelli, A.A.* ; Christensen, K.* ; Kaprio, J.* ; van IJzendoorn, M.H.* ; Emeny, R.T.* ; Deary, I.J.* ; Franke, L.* ; Sebert, S.* ; McRae, A.F.* ; Spiro, A.* ; van Dongen, J.*

Epigenome-wide association study meta-analysis of wellbeing.

Clin. Epigenet. 18:181 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Wellbeing is associated with both behavioral phenotypes as well as several key life outcomes, such as health, employment, and coping with stressful events. These phenotypes associated with wellbeing could be potential indicators of differential epigenetic patterns between individuals that differ in their levels of wellbeing. We performed the largest epigenome-wide (EWAS) meta-analysis of wellbeing to date by combining whole blood DNA methylation data (Illumina 450K array) from 13 cohorts from Europe, Australia, and the USA (N = 10,757 participants). After correcting for smoking and BMI, no epigenome-wide significant methylation sites were identified. We tested whether a weighted methylation score (MS) based on leave-one-cohort-out EWAS meta-analysis summary statistics predicted wellbeing in an independent cohort, and whether prediction was significant over and above the polygenic score (PGS) for wellbeing. The MS was associated with wellbeing (variance explained = 0.22%, p = 0.03) and was no longer significant after adding the polygenic score (PGS; variance explained = 0.43%, p = 0.0046, MS; variance explained = 0.07%, p = 0.2842). We further compared DNA methylation levels in 16 pairs of monozygotic twins discordant for wellbeing. These analyses revealed no significant within-pair DNA methylation differences at the top-sites from the meta-analysis or in MS. Our results suggest that larger EWAS meta-analyses with uniform phenotype assessment are required to identify methylation sites associated with wellbeing.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Body-mass Index; Dna Methylation; Epigenetic Regulation; Variants; Tissue
ISSN (print) / ISBN 1868-7075
e-ISSN 1868-7083
Zeitschrift Clinical Epigenetics
Quellenangaben Band: 18, Heft: 1, Seiten: , Artikelnummer: 181 Supplement: ,
Verlag Springer
Verlagsort Berlin : Heidelberg
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Förderungen The European Research Council (ERC-COG WELL-BEING)