| Title: | Rare genetic associations with human lifespan in UK Biobank are enriched for oncogenic genes |
| Journal: | Nature Communications |
| Published: | 28 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40021682/ |
| DOI: | https://doi.org/10.1038/s41467-025-57315-6 |
Publication 15678
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Abstract
Human lifespan is shaped by genetic and environmental factors. To enable precision health, understanding how genetic variants influence mortality is essential. We conducted a survival analysis in European ancestry participants of the UK Biobank, using age-at-death (N=35,551) and last-known-age (N=358,282). The associations identified were predominantly driven by cancer. We found lifespan-associated loci (APOE, ZSCAN23) for common variants and six genes where burden of loss-of-function variants were linked to reduced lifespan (TET2, ATM, BRCA2, CKMT1B, BRCA1, ASXL1). Additionally, eight genes with pathogenic missense variants were associated with reduced lifespan (DNMT3A, SF3B1, TET2, PTEN, SOX21, TP53, SRSF2, RLIM). Many of these genes are involved in oncogenic pathways and clonal hematopoiesis. Our findings highlight the importance of understanding genetic factors driving the most prevalent causes of mortality at a population level, highlighting the potential of early genetic testing to identify germline and somatic variants increasing one's susceptibility to cancer and/or early death.</p>
19 Keywords
- Adult
- Aged
- Aged, 80 and over
- Biological Specimen Banks
- Female
- Genetic Predisposition to Disease
- Genetic Variation
- Genome-Wide Association Study
- Humans
- Longevity
- Male
- Middle Aged
- Neoplasms
- Oncogenes
- Polymorphism, Single Nucleotide
- Survival Analysis
- UK Biobank
- United Kingdom
- White People
5 Authors
- Junyoung Park
- Andrés Peña-Tauber
- Lia Talozzi
- Michael D. Greicius
- Yann Le Guen
1 Application
| Application ID | Title |
|---|---|
| 45420 | Molecular underpinnings of resting-state fMRI |
Enabling scientific discoveries that improve human health