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| PMID |
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| TITLE |
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| Epigenome-wide association study meta-analysis of wellbeing. |
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| ABSTRACT |
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| 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. |
| © 2026. The Author(s). |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2025/05/13 |
| accepted |
2026/07/06 |
| medline |
2026/07/15 06:35 |
| pubmed |
2026/07/15 06:35 |
| entrez |
2026/07/15 00:13 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Bartels M |
|
Bartels |
Meike |
M |
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Amsterdam Public Health Research Institute, Amsterdam University Medical Centre, Amsterdam, The Netherlands. |
| van de Weijer MP |
|
van de Weijer |
Margot P |
MP |
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Department of Psychiatry, Location AMC, Amsterdam University Medical Centre, Amsterdam, The Netherlands. |
| Azcona-Granada N |
|
Azcona-Granada |
Natalia |
N |
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Amsterdam Public Health Research Institute, Amsterdam University Medical Centre, Amsterdam, The Netherlands. |
| Baselmans BML |
|
Baselmans |
Bart M L |
BML |
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Amsterdam Public Health Research Institute, Amsterdam University Medical Centre, Amsterdam, The Netherlands. |
| Suderman M |
|
Suderman |
Matthew |
M |
|
MRC Integrative Epidemiology Unit, Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK. |
| Soerensen M |
|
Soerensen |
Mette |
M |
|
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. |
| Buchwald J |
|
Buchwald |
Jadwiga |
J |
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Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. |
| Mulder RH |
|
Mulder |
Rosa H |
RH |
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Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. |
| Rawal R |
|
Rawal |
Rajesh |
R |
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Department of Microbiology, Laboratoire National de Santé, Dudelange, Luxembourg. |
| Luciano M |
|
Luciano |
Michelle |
M |
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Department of Psychology, University of Edinburgh, Edinburgh, UK. |
| Bonder MJ |
|
Bonder |
Marc Jan |
MJ |
|
Oncode Institute, Utrecht, The Netherlands. |
| Choudhary P |
|
Choudhary |
Priyanka |
P |
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Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland. |
| Lowry E |
|
Lowry |
Estelle |
E |
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Queen's University Belfast, Belfast, UK. |
| Lind PA |
|
Lind |
Penelope A |
PA |
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School of Biomedical Sciences, University of Queensland, Brisbane, Australia. |
| Schwartz J |
|
Schwartz |
Joel |
J |
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Department of Environmental Health, Harvard School of Public Health, Boston, USA. |
| Debrabant B |
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Debrabant |
Birgit |
B |
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Data Science and Statistics, Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark. |
| Ollikainen M |
|
Ollikainen |
Miina |
M |
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Minerva Foundation Institute for Medical Research, Helsinki, Finland. |
| Felix JF |
|
Felix |
Janine F |
JF |
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Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. |
| Bakermans-Kranenburg MJ |
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Bakermans-Kranenburg |
Marian J |
MJ |
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Faculty of Psychology and Humanities, Universidad San Sebastián, Valdivia, Chile. |
| Tiemeier H |
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Tiemeier |
Henning |
H |
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Department of Social and Behavioral Science, Harvard T.H. Chan School of Public Health, Boston, USA. |
| Gieger C |
|
Gieger |
Christian |
C |
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Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. |
| Waldenberger M |
|
Waldenberger |
Melanie |
M |
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Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
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Genetic Epidemiology, Brain and Mental Health Research Program, QIMR Berghofer, Brisbane, Australia. |
| Vokonas P |
|
Vokonas |
Pantel |
P |
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Veterans Affairs Boston Healthcare System, Boston, USA. |
| Baccarelli AA |
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Baccarelli |
Andrea A |
AA |
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Harvard T.H. Chan School of Public Health, Boston, USA. |
| Christensen K |
|
Christensen |
Kaare |
K |
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Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. |
| Kaprio J |
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Kaprio |
Jaakko |
J |
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Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. |
| van IJzendoorn MH |
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van IJzendoorn |
Marinus H |
MH |
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Psychiatry Monash Health, Monash University, Melbourne, Australia. |
| Emeny RT |
|
Emeny |
Rebecca T |
RT |
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Department of Internal Medicine, Division of Molecular Medicine, UNM Comprehensive Cancer Center, Cancer Control & Population Sciences Research Program, Albuquerque, USA. |
| Deary IJ |
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Deary |
Ian J |
IJ |
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Lothian Birth Cohorts, Psychology, University of Edinburgh, Edinburgh, UK. |
| Franke L |
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Franke |
Lude |
L |
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Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands. |
| Sebert S |
|
Sebert |
Sylvain |
S |
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Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland. |
| McRae AF |
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McRae |
Allan F |
AF |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. |
| Spiro A |
|
Spiro |
Avron |
A |
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Veterans Affairs Boston Healthcare System, Boston, USA. |
| van Dongen J |
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van Dongen |
Jenny |
J |
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Amsterdam Reproduction & Development (AR&D) Research Institute, Amsterdam, The Netherlands. j.van.dongen@vu.nl. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: Clinical epigenetics |
| ISOABBREVIATION: Clin Epigenetics |
| YEAR: 2026 |
| MONTH: Jul |
| DAY: 14 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1868-7083 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Clin Epigenetics |
| COUNTRY: Germany |
| ISSNLINKING: 1868-7075 |
| NLMUNIQUEID: 101516977 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GRANTID |
AGENCY |
COUNTRY |
| 771057 |
The European Research Council (ERC-COG WELL-BEING) |
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