ArticleNature communications2017
Identification and characterization of two functional variants in the human longevity gene FOXO3.
Erratum issuedOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
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57citing papers in PubMed, 2 pooled it
4.3field-weighted citation impact, top 5% of its field
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- A meta-analysis of genome-wide association studies identifies multiple longevity genes.Nature communications · 2019Pooled it
- Western Hunter-Gatherer genetic ancestry contributes to human longevity in the Italian population.GeroScience · 2026Article
- A Two-Hit Hypothesis for Chemotherapy-Induced Primary Ovarian Insufficiency in Asian Populations: A Population-Specific Mechanistic Framework Linking Genetic Susceptibility and Cytotoxic Stress via the PI3K-AKT-FOXO3 Axis.BioMed research international · 2026Review
- German longevity study reveals novel rare pro-longevity alleles clustering in mTOR signaling pathway.GeroScience · 2025Article
- The Protective Effect of FOXO3 rs2802292 G-Allele on Food Intake in a Southern Italian Cohort Affected by MASLD.Nutrients · 2025Article
- Review
- Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans.GeroScience · 2024Article
- Systems biology approaches identify metabolic signatures of dietary lifespan and healthspan across species.Nature communications · 2024Article
- Role of Phytochemicals in Treatment of Aging and Cancer: Focus on Mechanism of FOXO3 Activation.Antioxidants (Basel, Switzerland) · 2024Review
- Exploring the Relationship of rs2802292 with Diabetes and NAFLD in a Southern Italian Cohort-Nutrihep Study.International journal of molecular sciences · 2024Article
- Analysis of the aging-related biomarker in a nonhuman primate model using multilayer omics.BMC genomics · 2024Article
- [Genetics, epigenetics, and environmental factors in life expectancy-What role does nature-versus-nurture play in aging?]Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2024Review
- Article
- Genome-wide association study for stayability at different calvings in Nellore beef cattle.BMC genomics · 2024Article
- Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- Exploring the Relationship between the Gut Microbiota and Ageing: A Possible Age Modulator.International journal of environmental research and public health · 2023Review
- Assessment of Neuroanatomical Endophenotypes of Autism Spectrum Disorder and Association With Characteristics of Individuals With Schizophrenia and the General Population.JAMA psychiatry · 2023Article
- FOXO3A-short is a novel regulator of non-oxidative glucose metabolism associated with human longevity.Aging cell · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
34 authors at 9 institutions in 4 countries.
Friederike FlachsbartInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Janina DoseInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Liljana GentschewInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Claudia GeismannDepartment of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, 24105, Kiel, Germany.
Amke CaliebeInstitute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Brunswiker Straße 10, 24105, Kiel, Germany.
Carolin KnechtInstitute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Brunswiker Straße 10, 24105, Kiel, Germany.
Marianne NygaardThe Danish Aging Research Center, and the Danish Twin Registry, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, J. B. Winslows Vej 9B, 5000, Odense C, Denmark.
Nandini BadarinarayanInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Abdou ElSharawyInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Sandra MayInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Anne LuziusInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Guillermo G TorresInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Marlene JentzschInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Michael ForsterInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Robert HäslerInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Kathrin PallaufInstitute of Human Nutrition and Food Science, Kiel University, Hermann-Rodewald-Straße 6, 24118, Kiel, Germany.
Wolfgang LiebInstitute of Epidemiology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Niemannsweg 11, 24105, Kiel, Germany.
Céline DerboisCentre National de Recherche en Génomique Humaine CNRGH-CEA, 91000, Evry, France.
Pilar GalanUniversité Sorbonne Paris Cité-UREN, Unité de Recherche en Epidémiologie Nutritionnelle, U557 Inserm, U1125 Inra, Cnam, Université Paris 13, CRNH IdF, 93000, Bobigny, France.
Dmitriy DrichelDepartment of Statistical Genetics and Bioinformatics, Cologne Center for Genomics, University of Cologne, Weyertal 115b, 50931, Cologne, Germany.
Alexander ArltDepartment of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, 24105, Kiel, Germany.ORCID http://orcid.org/0000-0002-6160-1059
Andreas TillInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.ORCID http://orcid.org/0000-0002-0139-9143
Ben Krause-KyoraInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.ORCID http://orcid.org/0000-0001-9435-2872
Gerald RimbachInstitute of Human Nutrition and Food Science, Kiel University, Hermann-Rodewald-Straße 6, 24118, Kiel, Germany.
Hélène BlanchéFondation Jean Dausset-Centre d'Etude du Polymorphisme Humain (CEPH), 27 Rue Juliette Dodu, 75010, Paris, France.ORCID http://orcid.org/0000-0003-2115-575X
Jean-François DeleuzeCentre National de Recherche en Génomique Humaine CNRGH-CEA, 91000, Evry, France.
Lene ChristiansenThe Danish Aging Research Center, and the Danish Twin Registry, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, J. B. Winslows Vej 9B, 5000, Odense C, Denmark.
Kaare ChristensenThe Danish Aging Research Center, and the Danish Twin Registry, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, J. B. Winslows Vej 9B, 5000, Odense C, Denmark.
Michael NothnagelDepartment of Statistical Genetics and Bioinformatics, Cologne Center for Genomics, University of Cologne, Weyertal 115b, 50931, Cologne, Germany.
Philip RosenstielInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Stefan SchreiberInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Andre FrankeInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.ORCID http://orcid.org/0000-0003-1530-5811
Susanne SebensInstitute for Experimental Cancer Research, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, 24105, Kiel, Germany.
Almut NebelInstitute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany. a.nebel@mucosa.de.
Christian-Albrechts-Universität zu Kiel · DEUniversity of Southern Denmark · DKCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRUniversity Hospital Schleswig-Holstein · DEUniversity of Cologne · DEDamietta University · EGFondation Jean Dausset-CEPH · FRInserm · FRUniversity of Bonn · DE
Funding
TRAJECTORIES OF MORTALITY IN CAENORHABDITIS ELEGANSP01AG008761 · NIA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI YASHIN, ANATOLIY I · 1990 to 2008
$17.5MNIA NIH HHS P01 AG008761
Abstract
FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs. Specifically, in luciferase reporter assays, the longevity alleles of both variants show considerable enhancer activities that are reversed by IGF-1 treatment. An eQTL database search reveals that the alleles are also associated with higher FOXO3 mRNA expression in various human tissues, which is in line with observations in long-lived model organisms. In summary, we present experimental evidence for a functional link between common intronic variants in FOXO3 and human longevity.
Indexed as
AgedAged, 80 and overAge FactorsAllelesCCCTC-Binding FactorComputer SimulationFemaleForkhead Box Protein O3HaplotypesHumansInsulin-Like Growth Factor IIntronsLongevityMaleMiddle AgedPolymorphism, Single NucleotideCCCTC-Binding FactorCTCF protein, humanForkhead Box Protein O3FOXO3 protein, humanIGF1 protein, humanInsulin-Like Growth Factor IRNA, MessengerSerum Response FactorSRF protein, human
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