A methylation study of long-term depression risk

Shaunna L. Clark, Mohammad W. Hattab, Robin F. Chan, Andrey A. Shabalin, Laura K. M. Han, Min Zhao, Johannes H. Smit, Rick Jansen, Yuri Milaneschi, Lin Ying Xie, Gerard van Grootheest, Brenda W. J. H. Penninx, Karolina A. Aberg, Edwin J. C. G. van den Oord

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Recurrent and chronic major depressive disorder (MDD) accounts for a substantial part of the disease burden because this course is most prevalent and typically requires long-term treatment. We associated blood DNA methylation profiles from 581 MDD patients at baseline with MDD status 6 years later. A resampling approach showed a highly significant association between methylation profiles in blood at baseline and future disease status (P = 2.0 × 10−16). Top MWAS results were enriched specific pathways, overlapped with genes found in GWAS of MDD disease status, autoimmune disease and inflammation, and co-localized with eQTLS and (genic enhancers of) of transcription sites in brain and blood. Many of these findings remained significant after correction for multiple testing. The major themes emerging were cellular responses to stress and signaling mechanisms linked to immune cell migration and inflammation. This suggests that an immune signature of treatment-resistant depression is already present at baseline. We also created a methylation risk score (MRS) to predict MDD status 6 years later. The AUC of our MRS was 0.724 and higher than risk scores created using a set of five putative MDD biomarkers, genome-wide SNP data, and 27 clinical, demographic and lifestyle variables. Although further studies are needed to examine the generalizability to different patient populations, these results suggest that methylation profiles in blood may present a promising avenue to support clinical decision making by providing empirical information about the likelihood MDD is chronic or will recur in the future.
Original languageEnglish
JournalMolecular Psychiatry
DOIs
Publication statusE-pub ahead of print - 9 Sep 2019

Cite this

Clark, S. L., Hattab, M. W., Chan, R. F., Shabalin, A. A., Han, L. K. M., Zhao, M., ... van den Oord, E. J. C. G. (2019). A methylation study of long-term depression risk. Molecular Psychiatry. https://doi.org/10.1038/s41380-019-0516-z
Clark, Shaunna L. ; Hattab, Mohammad W. ; Chan, Robin F. ; Shabalin, Andrey A. ; Han, Laura K. M. ; Zhao, Min ; Smit, Johannes H. ; Jansen, Rick ; Milaneschi, Yuri ; Xie, Lin Ying ; van Grootheest, Gerard ; Penninx, Brenda W. J. H. ; Aberg, Karolina A. ; van den Oord, Edwin J. C. G. / A methylation study of long-term depression risk. In: Molecular Psychiatry. 2019.
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abstract = "Recurrent and chronic major depressive disorder (MDD) accounts for a substantial part of the disease burden because this course is most prevalent and typically requires long-term treatment. We associated blood DNA methylation profiles from 581 MDD patients at baseline with MDD status 6 years later. A resampling approach showed a highly significant association between methylation profiles in blood at baseline and future disease status (P = 2.0 × 10−16). Top MWAS results were enriched specific pathways, overlapped with genes found in GWAS of MDD disease status, autoimmune disease and inflammation, and co-localized with eQTLS and (genic enhancers of) of transcription sites in brain and blood. Many of these findings remained significant after correction for multiple testing. The major themes emerging were cellular responses to stress and signaling mechanisms linked to immune cell migration and inflammation. This suggests that an immune signature of treatment-resistant depression is already present at baseline. We also created a methylation risk score (MRS) to predict MDD status 6 years later. The AUC of our MRS was 0.724 and higher than risk scores created using a set of five putative MDD biomarkers, genome-wide SNP data, and 27 clinical, demographic and lifestyle variables. Although further studies are needed to examine the generalizability to different patient populations, these results suggest that methylation profiles in blood may present a promising avenue to support clinical decision making by providing empirical information about the likelihood MDD is chronic or will recur in the future.",
author = "Clark, {Shaunna L.} and Hattab, {Mohammad W.} and Chan, {Robin F.} and Shabalin, {Andrey A.} and Han, {Laura K. M.} and Min Zhao and Smit, {Johannes H.} and Rick Jansen and Yuri Milaneschi and Xie, {Lin Ying} and {van Grootheest}, Gerard and Penninx, {Brenda W. J. H.} and Aberg, {Karolina A.} and {van den Oord}, {Edwin J. C. G.}",
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A methylation study of long-term depression risk. / Clark, Shaunna L.; Hattab, Mohammad W.; Chan, Robin F.; Shabalin, Andrey A.; Han, Laura K. M.; Zhao, Min; Smit, Johannes H.; Jansen, Rick; Milaneschi, Yuri; Xie, Lin Ying; van Grootheest, Gerard; Penninx, Brenda W. J. H.; Aberg, Karolina A.; van den Oord, Edwin J. C. G.

In: Molecular Psychiatry, 09.09.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Clark, Shaunna L.

AU - Hattab, Mohammad W.

AU - Chan, Robin F.

AU - Shabalin, Andrey A.

AU - Han, Laura K. M.

AU - Zhao, Min

AU - Smit, Johannes H.

AU - Jansen, Rick

AU - Milaneschi, Yuri

AU - Xie, Lin Ying

AU - van Grootheest, Gerard

AU - Penninx, Brenda W. J. H.

AU - Aberg, Karolina A.

AU - van den Oord, Edwin J. C. G.

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