ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2021
Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Polygenic scores for longevity in relation to brain MRI measures in a cohort of 70-year-olds.npj aging · 2026Article
- Biological aging and generational shifts in early-onset cancer risk.Nature medicine · 2026Article
- Genetic predisposition to longer lifespan, lifestyle factors, and all-cause mortality: a 17-year prospective cohort study.GeroScience · 2026Article
- Modifiable risk factors attenuated longevity genetic predisposition on life expectancy in the oldest old.npj aging · 2026Article
- Genetic testing of common and rare variants in dementia patients from a memory clinic : Dementia-related genetic testing in memory clinic.Alzheimer's research & therapy · 2025Article
- A centenarian single nucleotide polymorphism in collagen gene COL25A1 promotes longevity in C. elegans.npj aging · 2025Article
- The association of a polygenic lifespan score with the risk of common age-related diseases and mortality.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- SNP rs6543176 is associated with extreme human longevity but increased risk for cancer.GeroScience · 2025Article
- Self-rated health and mortality: family background and genetic precursors.Discover social science and health · 2025Article
- Genetic Prediction Modeling in Large Cohort Studies via Boosting Targeted Loss Functions.Statistics in medicine · 2024Article
- All-Cause Mortality and Cause-Specific Death in U.S. Long-Lived Siblings: Data From the Long Life Family Study.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- The relationship between 11 different polygenic longevity scores, parental lifespan, and disease diagnosis in the UK Biobank.GeroScience · 2024Article
- Cognitively healthy centenarians are genetically protected against Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Polygenic Propensity for Longevity, APOE-ε4 Status, Dementia Diagnosis, and Risk for Cause-Specific Mortality: A Large Population-Based Longitudinal Study of Older Adults.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
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- High polygenic risk score for exceptional longevity is associated with a healthy metabolic profile.GeroScience · 2023Article
- Article
- Optimizing Translational Research for Exceptional Health and Life Span: A Systematic Narrative of Studies to Identify Translatable Therapeutic Target(s) for Exceptional Health Span in Humans.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Long-Lived Individuals Show a Lower Burden of Variants Predisposing to Age-Related Diseases and a Higher Polygenic Longevity Score.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases.
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