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

Autor: Tamman AJF; Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA. amanda.tamman@bcm.edu., Koller D; Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA., Nagamatsu S; Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA., Cabrera-Mendoza B; Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA., Abdallah C; Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA., Krystal JH; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA., Gelernter J; Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA., Montalvo-Ortiz JL; Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA., Polimanti R; Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA., Pietrzak RH; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA.; Department of Social and Behavioral Sciences, Yale School of Public Health, New Haven, CT, USA.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2024 Mar; Vol. 49 (4), pp. 699-708. Date of Electronic Publication: 2023 Oct 17.
DOI: 10.1038/s41386-023-01747-5
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)
Databáze: MEDLINE
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