Association between the Epigenetic Lifespan Predictor GrimAge and History of Suicide Attempt in Bipolar Disorder

Abstract

Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n=50), BD individuals with (n=77, BD/SA) and without (n=67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n=48) and BD/non-SA (n=47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F=5.424, p=0.005), with the highest GrimAgeAccel in BD/SA (p=0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p=0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was supported by the National Institute of Mental Health (NIMH, K01 MH121580 to GRF), the American Foundation for Suicide Prevention (YIG-0-066-20 to GRF), and the Baszucki Research Foundation (GRF). Translational Psychiatry Program (USA) is funded by the Department of Psychiatry and Behavioral Sciences, McGovern Medical School at UTHealth. This study was also supported by an EHSRC Career Enhancement award and an EHSRC Pilot grant (NIH P30 ES005605) awarded to MEG, and an Iowa Neuroscience Institute Research Program of Excellence grant with philanthropy from the Roy J. Carver Charitable Trust. Research reported in this publication for the University of Iowa was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002537) and the National Institute of Mental Health (NIMH R01MH125838 to VAM and JAW). APD is supported by a 2020 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the American Foundation for Suicide Prevention, or the Baszucki Research Foundation.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The protocol for the study was approved by the local institutional review board at the University of Texas Health Science Center at Houston (IRB, HSC-MS-09-0340) and at the University of Iowa (IRB, 201708703).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

留言 (0)

沒有登入
gif