Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model

  1. Emeny, Rebecca T.
  2. Baumert, Jens
  3. Zannas, Anthony S.
  4. Kunze, Sonja
  5. Wahl, Simone
  6. Iurato, Stella
  7. Arloth, Janine
  8. Erhardt, Angelika
  9. Balsevich, Georgia
  10. Schmidt, Mathias V.
  11. Weber, Peter
  12. Kretschmer, Anja
  13. Pfeiffer, Liliane
  14. Kruse, Johannes
  15. Strauch, Konstantin
  16. Roden, Michael
  17. Herder, Christian ORCID logo
  18. Koenig, Wolfgang
  19. Gieger, Christian
  20. Waldenberger, Melanie
  21. Peters, Annette
  22. Binder, Elisabeth B.
  23. Ladwig, Karl-Heinz

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1000 Titel
  • Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model
1000 Autor/in
  1. Emeny, Rebecca T. |
  2. Baumert, Jens |
  3. Zannas, Anthony S. |
  4. Kunze, Sonja |
  5. Wahl, Simone |
  6. Iurato, Stella |
  7. Arloth, Janine |
  8. Erhardt, Angelika |
  9. Balsevich, Georgia |
  10. Schmidt, Mathias V. |
  11. Weber, Peter |
  12. Kretschmer, Anja |
  13. Pfeiffer, Liliane |
  14. Kruse, Johannes |
  15. Strauch, Konstantin |
  16. Roden, Michael |
  17. Herder, Christian |
  18. Koenig, Wolfgang |
  19. Gieger, Christian |
  20. Waldenberger, Melanie |
  21. Peters, Annette |
  22. Binder, Elisabeth B. |
  23. Ladwig, Karl-Heinz |
1000 Erscheinungsjahr 2017
1000 LeibnizOpen
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2017-05-27
1000 Erschienen in
1000 Quellenangabe
  • 43:342–353
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2018
1000 Lizenz
1000 Verlagsversion
  • http://doi.org/10.1038/npp.2017.102 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729551/ |
1000 Ergänzendes Material
  • https://www.nature.com/articles/npp2017102#supplementary-information |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32–72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (β-coefficient=0.56 standard error (SE)=0.10, p (Bonferroni)=0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p=0.083) and a significant interaction among women (p=0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (β=0.005, SE=0.002, p=0.021, n=131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p=0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress-responsive Asb1 gene in anxiety-related phenotypes. Further studies are necessary to elucidate the causal direction of this association and the potential role of Asb1-mediated immune dysregulation in anxiety disorders.
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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