Journal article
Integrating the environmental and genetic architectures of aging and mortality
- Abstract:
- Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging. These exposures were also associated with incident age-related multimorbidity, aging biomarkers and major disease risk factors. Compared with information on age and sex, polygenic risk scores for 22 major diseases explained less than 2 percentage points of additional mortality variation, whereas the exposome explained an additional 17 percentage points. Polygenic risk explained a greater proportion of variation (10.3-26.2%) compared with the exposome for incidence of dementias and breast, prostate and colorectal cancers, whereas the exposome explained a greater proportion of variation (5.5-49.4%) compared with polygenic risk for incidence of diseases of the lung, heart and liver. Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and incidence of common age-related diseases, suggesting that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41591-024-03483-9
Authors
+ European Commission
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- Funder identifier:
- https://ror.org/00k4n6c32
- Grant:
- 873749
- Programme:
- Horizon 2020
+ Wellcome Trust
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- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 203141/Z/16/Z
- 223100/Z/21/Z
+ British Heart Foundation
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- Funder identifier:
- https://ror.org/02wdwnk04
- Grant:
- RE/18/3/34214
- Publisher:
- Springer Nature
- Journal:
- Nature Medicine More from this journal
- Volume:
- 31
- Issue:
- 3
- Pages:
- 1016-1025
- Place of publication:
- United States
- Publication date:
- 2025-02-19
- Acceptance date:
- 2024-12-18
- DOI:
- EISSN:
-
1546-170X
- ISSN:
-
1078-8956
- Pmid:
-
39972219
- Language:
-
English
- Pubs id:
-
2090908
- Local pid:
-
pubs:2090908
- Deposit date:
-
2025-03-12
- ARK identifier:
Terms of use
- Copyright holder:
- Argentieri et al.
- Copyright date:
- 2025
- Rights statement:
- © The Author(s) 2025, corrected publication 2025. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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