ArticlePloS one2012
Genetic signatures of exceptional longevity in humans.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers, 9 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
220 citing papers in PubMed, 9 syntheses or guidelines pooled it, 461 citations in OpenAlex.
- TOMM40 genetic variants associated with healthy aging and longevity: a systematic review.BMC geriatrics · 2022Pooled it
- Taste receptor polymorphisms and longevity: a systematic review and meta-analysis.Aging clinical and experimental research · 2021Pooled it
- APOE Alleles and Extreme Human Longevity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2019Pooled it
- Effects of FOXO3 Polymorphisms on Survival to Extreme Longevity in Four Centenarian Studies.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018Pooled it
- Limitations and risks of meta-analyses of longevity studies.Mechanisms of ageing and development · 2017Pooled it
- The transcriptional landscape of age in human peripheral blood.Nature communications · 2015Pooled it
- GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.The journals of gerontology. Series A, Biological sciences and medical sciences · 2015Pooled it
- Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age.Human molecular genetics · 2014Pooled it
- Pooled it
- Socioeconomic Status and Poor Health Outcome at 10 Years of Follow-Up in the Multi-Ethnic Study of Atherosclerosis.PloS one · 2016Trial
- Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and next-generation sequencing.Mechanisms of ageing and development · 2013Trial
- Genetic links between multimorbidity and human aging.GeroScience · 2026Article
- Why Some People Live Past 100: The Role of the Immune System in Centenarians, Semi-Supercentenarians and Supercentenarians.International journal of molecular sciences · 2026Review
- Exceptional Parental Longevity and Onset of Morbidity and Mortality Across Cohorts.JAMA network open · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- DREAM repressive activity links somatic mutation, lifespan and disease.Nature aging · 2026Article
- A multi-omic atlas in the African turquoise killifish reveals increased glucocorticoid signaling as a hallmark of brain aging.bioRxiv : the preprint server for biology · 2026Article
- The apolipoprotein gene: a modulating role on brain volume and cognitive function in carriers of the fragile X premutation.Neurobiology of disease · 2026Article
- Genetic, Socioecological, and Health Research on Extreme Longevity in Semisupercentenarians and Supercentenarians: A Scoping Review.Journal of aging research · 2026Article
- Relationship between vitamin D and surrogate parameters (leukocyte telomerase length, telomerase activity), and genes (Frontiers in endocrinology · 2026Article
160 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different "genetic signatures" of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity.
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Registered trials
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.