ArticlePLoS genetics2015
Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
79 citing papers in PubMed, 3 syntheses or guidelines pooled it, 177 citations in OpenAlex.
- TOMM40 genetic variants associated with healthy aging and longevity: a systematic review.BMC geriatrics · 2022Pooled it
- Strong impact of natural-selection-free heterogeneity in genetics of age-related phenotypes.Aging · 2018Pooled it
- Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.Nature communications · 2017Pooled it
- Cardiac Function Improvement and Bone Marrow Response -: Outcome Analysis of the Randomized PERFECT Phase III Clinical Trial of Intramyocardial CD133EBioMedicine · 2017Trial
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- Article
- Mitochondrial protein import stress causes lysosomal damage and progressive tissue atrophy.EMBO reports · 2026Article
- Genetic architecture of human aging and longevity: Insights from genome-wide association studies.BMB reports · 2026Review
- Genetic, Socioecological, and Health Research on Extreme Longevity in Semisupercentenarians and Supercentenarians: A Scoping Review.Journal of aging research · 2026Article
- A centenarian single nucleotide polymorphism in collagen gene COL25A1 promotes longevity in C. elegans.npj aging · 2025Article
- Analysis of lifespan across diversity outbred mouse studies identifies multiple longevity-associated loci.Genetics · 2025Article
- Multiomics Analysis of a Micronutrient-Rich Dietary Pattern and the Aging Genotype 9p21 on the Plasma Proteome of Young Adults.Nutrients · 2025Article
- Clinical and neuropathological analysis of Down syndrome over 7 decades of life.Journal of neuropathology and experimental neurology · 2025Article
- TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging.Aging brain · 2025Article
- The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age.Mechanisms of ageing and development · 2024Article
- Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets.Cell death discovery · 2024Review
- Targeted sequencing of the 9p21.3 region reveals association with reduced disease risks in Ashkenazi Jewish centenarians.Aging cell · 2023Article
- Article
- Applications of multi-omics analysis in human diseases.MedComm · 2023Review
- Aging Hallmarks and the Role of Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
19 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
11 authors at 7 institutions in 2 countries.
Funding
Abstract
We developed a new statistical framework to find genetic variants associated with extreme longevity. The method, informed GWAS (iGWAS), takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity. To gain support for our approach, we first show there is an overlap between loci involved in disease and loci associated with extreme longevity. These results indicate that several disease variants may be depleted in centenarians versus the general population. Next, we used iGWAS to harness information from 14 meta-analyses of disease and trait GWAS to identify longevity loci in two studies of long-lived humans. In a standard GWAS analysis, only one locus in these studies is significant (APOE/TOMM40) when controlling the false discovery rate (FDR) at 10%. With iGWAS, we identify eight genetic loci to associate significantly with exceptional human longevity at FDR < 10%. We followed up the eight lead SNPs in independent cohorts, and found replication evidence of four loci and suggestive evidence for one more with exceptional longevity. The loci that replicated (FDR < 5%) included APOE/TOMM40 (associated with Alzheimer's disease), CDKN2B/ANRIL (implicated in the regulation of cellular senescence), ABO (tags the O blood group), and SH2B3/ATXN2 (a signaling gene that extends lifespan in Drosophila and a gene involved in neurological disease). Our results implicate new loci in longevity and reveal a genetic overlap between longevity and age-related diseases and traits, including coronary artery disease and Alzheimer's disease. iGWAS provides a new analytical strategy for uncovering SNPs that influence extreme longevity, and can be applied more broadly to boost power in other studies of complex phenotypes.
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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.