| Title: | Association between biological aging and genetic susceptibility with the risk of bipolar disorder and schizophrenia: A prospective cohort study |
| Journal: | Journal of Affective Disorders |
| Published: | 30 Oct 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41173105/ |
| DOI: | https://doi.org/10.1016/j.jad.2025.120568 |
Publication 19113
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Abstract
BACKGROUND: Bipolar disorder (BD) and schizophrenia (SCZ) are severe psychiatric disorders with complex etiologies. Accelerated biological aging, potentially exacerbated by environmental exposures like air pollution, may represent a key pathogenic mechanism. This study aimed to investigate the independent and combined effects of biological aging and genetic risk on incident BD and SCZ, and to assess whether biological aging mediates the impact of environmental factors.</p>
METHODS: We analyzed data from 483,482 UK Biobank participants. Biological aging was quantified using phenotypic age acceleration (PhenoAgeAccel), and genetic predisposition was assessed via polygenic risk scores (PRSs). Cox proportional hazards models, adjusted for numerous covariates, were used to estimate hazard ratios (HRs). Mediation analysis evaluated the role of PhenoAgeAccel in the pathway from air pollution and noise to disease outcomes.</p>
RESULTS: A 5-year increase in PhenoAgeAccel was significantly associated with a higher risk of BD (HR 1.271, 95 % CI 1.185-1.362) and SCZ (HR 1.348, 95 % CI 1.230-1.476). The association with BD risk was stronger in overweight or obese participants. Individuals with high genetic risk and greater biological aging had the highest risk of developing BD (HR 2.492, 95 % CI 1.764-3.521) and SCZ (HR 7.795, 95 % CI 3.913-15.529). PhenoAgeAccel mediated 7-12 % of the association between air pollution and BD and 3-5 % of its association with SCZ.</p>
CONCLUSION: PhenoAgeAccel is significantly associated with the risk of common psychiatric disorders, including BD and SCZ, and shows promise as a novel biomarker to guide precision prevention and management of these conditions.</p>
15 Keywords
- Adult
- Aged
- Aging
- Air Pollution
- Bipolar Disorder
- Female
- Genetic Predisposition to Disease
- Humans
- Male
- Middle Aged
- Proportional Hazards Models
- Prospective Studies
- Risk Factors
- Schizophrenia
- United Kingdom
9 Authors
- Weidong Ji
- Yushan Zhang
- Yinlin Cheng
- Cong Lai
- Jiaqi Chen
- Ruiqi Feng
- Huiying Zhao
- Kai Wang
- Zhensheng Hu
1 Application
| Application ID | Title |
|---|---|
| 51732 | Genetic studies of Hereditary Hearing Loss |
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