SynthesisAging cell2011
Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited.
Synthesis in Aging cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 13 of them syntheses that pooled 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.
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
175 citing papers in PubMed, 13 syntheses or guidelines pooled it, 284 citations in OpenAlex.
- A Prospective Analysis of Genetic Variants Associated with Human Lifespan.G3 (Bethesda, Md.) · 2019Pooled it
- A meta-analysis of genome-wide association studies identifies multiple longevity genes.Nature communications · 2019Pooled it
- Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.PLoS medicine · 2019Pooled it
- APOE Alleles and Extreme Human Longevity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2019Pooled it
- Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.Nature communications · 2017Pooled it
- Limitations and risks of meta-analyses of longevity studies.Mechanisms of ageing and development · 2017Pooled it
- New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.Nature communications · 2016Pooled 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
- Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals.Human molecular genetics · 2013Pooled it
- Pooled it
- A genome-wide association study of aging.Neurobiology of aging · 2011Pooled it
- 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
- Alzheimer's disease-like brain pattern biomarker: capturing risks and predicting disease onset.Molecular psychiatry · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Discovery-Driven Plasma Proteomics Identifies a Multi-Protein Signature for Amyloid PET Positivity: A Machine Learning Analysis of the Bio-Hermes Cohort.International journal of molecular sciences · 2026Article
- Article
- Low genetic risk for coronary artery disease underlies multigenerational longevity and healthy aging.GeroScience · 2026Article
- Genome-wide association study and pathway analysis of healthy aging in Super Seniors.GeroScience · 2026Article
115 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
28 authors at 7 institutions in 4 countries.
Funding
Abstract
By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Study (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study, and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P<1×10(-4) ) showed genome-wide significance with survival into old age in the meta-analysis of 4149 nonagenarian cases and 7582 younger controls [OR=0.71 (95% CI 0.65-0.77), P=3.39 × 10(-17) ]. This SNP, rs2075650, is located in TOMM40 at chromosome 19q13.32 close to the apolipoprotein E (APOE) gene. Although there was only moderate linkage disequilibrium between rs2075650 and the ApoE ε4 defining SNP rs429358, we could not find an APOE-independent effect of rs2075650 on longevity, either in cross-sectional or in longitudinal analyses. As expected, rs429358 associated with metabolic phenotypes in the offspring of the nonagenarian cases from the LLS and their partners. In addition, we observed a novel association between this locus and serum levels of IGF-1 in women (P=0.005). In conclusion, the major locus determining familial longevity up to high age as detected by GWAS was marked by rs2075650, which tags the deleterious effects of the ApoE ε4 allele. No other major longevity locus was found.
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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.