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Genetic trade‐offs between complex diseases and longevity
Abstract
Longevity was influenced by many complex diseases and traits. However, the relationships between human longevity and genetic risks of complex diseases were not broadly studied. Here, we constructed polygenic risk scores (PRSs) for 225 complex diseases/traits and evaluated their relationships with human longevity in a cohort with 2178 centenarians and 2299 middle‐aged individuals. Lower genetic risks of stroke and hypotension were observed in centenarians, while higher genetic risks of schizophrenia (SCZ) and type 2 diabetes (T2D) were detected in long‐lived individuals. We further stratified PRSs into cell‐type groups and significance‐level groups. The results showed that the immune component of SCZ genetic risk was positively linked to longevity, and the renal component of T2D genetic risk was the most deleterious. Additionally, SNPs with very small p‐values (p ≤ 1x10‐5) for SCZ and T2D were negatively correlated with longevity. While for the less significant SNPs (1x10‐5 < p ≤ 0.05), their effects on disease and longevity were positively correlated. Overall, we identified genetically informed positive and negative factors for human longevity, gained more insights on the accumulation of disease risk alleles during evolution, and provided evidence for the theory of genetic trade‐offs between complex diseases and longevity.
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Disease risk reduces lifespan via shared biological pathways.
“This is aligned with previous findings and reinforces the hypothesis that disease risk reduces lifespan via shared biological pathways45–47.”
From Genetic trade-offs in fertility and longevity explain the maintenance of disease-associated alleles in humans (2026) · cites this paper as [47]
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Brigos-Barril, E., Vasallo, C., Farré, X., Morcillo-Suárez, C., Polo-Alonso, S., Rodríguez-Fernández, B., Valenzuela, A., Sarabia, C., Bosch, E., Laayouni, H., et al. (2026) · Nature Ecology & Evolution · doi:10.1038/s41559-026-03140-z · Cited by 6
Metadata
- Authors
- Hu, D., Li, Y., Zhang, D., Ding, J., Song, Z., Min, J., Zeng, Y., & Nie, C.
- Affiliations
- College of Life Sciences University of Chinese Academy of Sciences Beijing China
- BGI‐Shenzhen Shenzhen China
- The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine Zhejiang University Hangzhou China
- Center for Healthy Aging and Development Studies, National School of Development Peking University Beijing China
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2022-06-26
- Volume
- 21
- Issue
- 7
- ISSN
- 1474-9718
- 1474-9726
- PMC
- PMC9282840
- Cited by
- 13
- References
- 11
- Language
- en
- Funders
- National Key Research and Development Program of China (2020YFC2002902, 2018YFC2000400)
- National Natural Science Foundation of China (81941025, 72061137004)
- National Institutes of Health (P01AG031719)
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