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Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge

Neuropsychopharmacology volume 49, pages 699–708 (2024)Cite this article

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A Correction to this article was published on 05 January 2024

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Abstract

GrimAge acceleration has previously predicted age-related morbidities and mortality. In the current study, we sought to examine how GrimAge is associated with genetic predisposition for systemic inflammation and whether psychosocial factors moderate this association. Military veterans from the National Health and Resilience in Veterans study, which surveyed a nationally representative sample of European American male veterans, provided saliva samples for genotyping (N = 1135). We derived polygenic risk scores (PRS) from the UK Biobank as markers of genetic predisposition to inflammation. Results revealed that PRS for three inflammatory PRS markers—HDL (lower), apolipoprotein B (lower), and gamma-glutamyl transferase (higher)—were associated with accelerated GrimAge. Additionally, these PRS interacted with a range of potentially modifiable psychosocial variables, such as exercise and gratitude, previously identified as associated with accelerated GrimAge. Using gene enrichment, we identified anti-inflammatory and antihistamine drugs that perturbate pathways of genes highly represented in the inflammatory PRS, laying the groundwork for future work to evaluate the potential of these drugs in mitigating epigenetic aging.

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Fig. 1: Scatterplots for PRS x environment interactions.

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Funding

RP would like to acknowledge the following funding sources: Horizon 2020 Marie Sklodowska-Curie Individual Fellowship (101028810), the National Institutes of Drug Abuse (R33 DA047527), the National Institute of Mental Health (RF1 MH132337).

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Authors and Affiliations

  1. Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA

    Amanda J. F. Tamman & Chadi Abdallah

  2. Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA

    Dora Koller, Sheila Nagamatsu, Brenda Cabrera-Mendoza, Joel Gelernter, Janitza L. Montalvo-Ortiz & Renato Polimanti

  3. Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA

    Dora Koller, Sheila Nagamatsu, Brenda Cabrera-Mendoza, Chadi Abdallah, John H. Krystal, Joel Gelernter, Janitza L. Montalvo-Ortiz, Renato Polimanti & Robert H. Pietrzak

  4. U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA

    John H. Krystal, Joel Gelernter, Janitza L. Montalvo-Ortiz & Robert H. Pietrzak

  5. Department of Social and Behavioral Sciences, Yale School of Public Health, New Haven, CT, USA

    Robert H. Pietrzak

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  1. Amanda J. F. Tamman
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  2. Dora Koller
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  10. Robert H. Pietrzak
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Contributions

Formal analysis: AJFT, DK, RP, and SN; Investigation: RHP; Resources: RHP; Writing – original draft: AJFT, DK, and RHP; Visualization: AJFT, DK, and RHP; Writing – review and editing: RHP, JK, JG, JLMO, SN, CA, RP, and BCM; Supervision: RHP; Funding acquisition: RHP; Conceptualization: JK, AJFT, and RHP; Methodology: RP and JG.

Corresponding author

Correspondence to Amanda J. F. Tamman.

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This manuscript contains original research, has not been published elsewhere and has not been submitted simultaneously for publication elsewhere. We have the following disclosures to report: JG is named as an inventor on PCT patent application #15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. JG and RP are paid for their editorial work on the journal Complex Psychiatry. RP received a research grant from Alkermes. JHK has served as a scientific consultant to the following companies (the Individual Consultant Agreements listed are less than $5000 per year): AMGEN; AstraZeneca Pharmaceuticals; Bigen, Idec, MA; Biomedisyn Corporation; Forum Pharmaceuticals; Janssen Research & Development; Otsuka America Pharmaceutical, Inc.; Sunovion Pharmaceuticals, Inc.; Takeda Industries; Taisho Pharmaceutical Co., Ltd. He is on the Scientific Advisory Board for the following companies: Biohaven Pharmaceuticals; Blackthorn Therapeutics,Inc.; Lohocla Research Corporation; Luc Therapeutics, Inc.; Pfizer Pharmaceuticals; TRImaran Pharma. He holds stock in Biohaven Pharmaceuticals Medical Sciences and stock options in Blackthorn Therapeutics, Inc. and Luc Therapeutics, Inc. He is the editor of Biological Psychiatry (Income greater than $10,000). CGA has served as a consultant and/or on advisory boards for Aptinyx, Genentech, Janssen, Psilocybin Labs, Lundbeck, Guidepoint, and FSV7, and as editor of Chronic Stress for Sage Publications, Inc. He also filed a patent for using mTORC1 inhibitors to augment the effects of antidepressants (Aug 20, 2018). AJFT, BCM, DK, RHP, SN, and JLMO reported no biomedical financial interest.

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Tamman, A.J.F., Koller, D., Nagamatsu, S. et al. Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge. Neuropsychopharmacol. 49, 699–708 (2024). https://doi.org/10.1038/s41386-023-01747-5

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