Evidence map›Paper›PMID 40021682›Full record

ArticleNature communications2025

Rare genetic associations with human lifespan in UK Biobank are enriched for oncogenic genes.

Junyoung Park, Andrés Peña-Tauber, Lia Talozzi, Michael D Greicius, Yann Le Guen

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Evolutionary genetics of ageing.Nature reviews. Genetics · 2026
    Review
  2. Review
  3. Observational
  4. Review
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Junyoung ParkDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA. jpark01@stanford.edu.ORCID http://orcid.org/0000-0002-9098-2858
Andrés Peña-TauberDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0001-9501-4920
Lia TalozziDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Michael D Greicius *Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Yann Le Guen *Quantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, CA, 94304, USA.ORCID http://orcid.org/0000-0001-6649-8364

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI MICHAEL KENNEY · 2007 to 2026
$71.4M
Stanford Center for Clinical and Translational Research and EducationUM1TR004921 · NCATS · STANFORD UNIVERSITY · PI MANISHA DESAI, DEAN W FELSHER · 2024 to 2026
$30.1M
NCATS NIH HHS UM1 TR004921NCI NIH HHS P30 CA124435
6 · The paper itself

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.

Indexed as

LongevityNeoplasmsOncogenesAdultAgedAged, 80 and overBiological Specimen BanksFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedSurvival AnalysisUK BiobankUnited KingdomWhite People

Identifiers

PMID40021682
PMCPMC11871019

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.