CoChat
Sign Up
Cited by 211Genetic Associations and EpidemiologyGenetics, Aging, and Longevity in Model OrganismsGenetics and Physical Performance

Human longevity: 25 genetic loci associated in 389,166 UK biobank participants

Open access
Pilling, Luke C., Kuo, Chia-Ling, Sicinski, Kamil, Tamosauskaite, Jone, Kuchel, George A., Harries, Lorna W., Herd, Pamela, Wallace, Robert +2 more·2017·Aging
DOI 10.18632/aging.101334PMC PMC5764389
Open this paper in CoChat — free account

Abstract

=1,181) in UK Biobank. The results suggest that human longevity is highly polygenic with prominent roles for loci likely involved in cellular senescence and inflammation, plus lipid metabolism and cardiovascular conditions. There may also be gender specific routes to longevity.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.18632/aging.101334

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Several studies of large populations of individuals from European ancestry have raised the possibility that APOE is a longevity gene, with the APOEε2 variant associated with longer survival and the APOEε4 with shorter survival in a dose-dependent manner.

    “Several studies of large populations of individuals from European ancestry have raised the possibility that APOE is a longevity gene, with the APOEε2 variant associated with longer survival and the APOEε4 with shorter survival in a dose-dependent manner90–94.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [91]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 39

  1. [1]Kenyon CJ The genetics of ageing Nature 2010 464 504 12 https://doi.org/10.1038/nature08980 20336132 · DOI · Paper page
  2. [2]Joshi PK Pirastu N Kentistou KA Fischer K Hofer E Schraut KE Clark DW Nutile T Barnes CL Timmers PR Shen X Gandin I McDaid AF Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity Nat Commun 2017 8 910 https://doi.org/10.1038/s41467-017-00934-5 29030599 PMC5715013 · DOI · Paper page
  3. [3]Broer L Buchman AS Deelen J Evans DS Faul JD Lunetta KL Sebastiani P Smith JA Smith AV Tanaka T Yu L Arnold AM Aspelund T GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy J Gerontol A Biol Sci Med Sci 2015 70 110 18 https://doi.org/10.1093/gerona/glu166 25199915 PMC4296168 · DOI
  4. [4]Deelen J Beekman M Uh HW Broer L Ayers KL Tan Q Kamatani Y Bennet AM Tamm R Trompet S Guðbjartsson DF Flachsbart F Rose G Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age Hum Mol Genet 2014 23 4420 32 https://doi.org/10.1093/hmg/ddu139 24688116 PMC4103672 · DOI
  5. [5]Fortney K Dobriban E Garagnani P Pirazzini C Monti D Mari D Atzmon G Barzilai N Franceschi C Owen AB Kim SK Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity PLoS Genet 2015 11 e1005728 https://doi.org/10.1371/journal.pgen.1005728 26677855 PMC4683064 · DOI
  6. [6]McDaid AF Joshi PK Porcu E Komljenovic A Li H Sorrentino V Litovchenko M Bevers RP Rüeger S Reymond A Bochud M Deplancke B Williams RW Bayesian association scan reveals loci associated with human lifespan and linked biomarkers Nat Commun 2017 8 15842 https://doi.org/10.1038/ncomms15842 28748955 PMC5537485 · DOI
  7. [7]Hjelmborg J vB Iachine I Skytthe A Vaupel JW McGue M Koskenvuo M Kaprio J Pedersen NL Christensen K Genetic influence on human lifespan and longevity Hum Genet 2006 119 312 21 https://doi.org/10.1007/s00439-006-0144-y 16463022 · DOI
  8. [8]Gudmundsson H Gudbjartsson DF Frigge M Gulcher JR Stefánsson K Inheritance of human longevity in Iceland Eur J Hum Genet 2000 8 743 49 https://doi.org/10.1038/sj.ejhg.5200527 11039573 · DOI
  9. [9]Dutta A Henley W Robine JM Langa KM Wallace RB Melzer D Longer lived parents: protective associations with cancer incidence and overall mortality J Gerontol A Biol Sci Med Sci 2013 68 1409 18 https://doi.org/10.1093/gerona/glt061 23685624 PMC3919622 · DOI
  10. [10]Dutta A Henley W Robine JM Llewellyn D Langa KM Wallace RB Melzer D Aging children of long-lived parents experience slower cognitive decline Alzheimers Dement 2014 10 S315 22 https://doi.org/10.1016/j.jalz.2013.07.002 24210527 · DOI
  11. [11]Atkins JL Pilling LC Ble A Dutta A Harries LW Murray A Brayne C Robine JM Kuchel GA Ferrucci L Melzer D Longer-Lived Parents and Cardiovascular Outcomes: 8-Year Follow-Up In 186,000 U.K. Biobank Participants J Am Coll Cardiol 2016 68 874 75 https://doi.org/10.1016/j.jacc.2016.05.072 27539182 PMC12159424 · DOI
  12. [12]Pilling LC Atkins JL Bowman K Jones SE Tyrrell J Beaumont RN Ruth KS Tuke MA Yaghootkar H Wood AR Freathy RM Murray A Weedon MN Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants Aging (Albany NY) 2016 8 547 60 https://doi.org/10.18632/aging.100930 27015805 PMC4833145 · DOI
  13. [13]Joshi PK Fischer K Schraut KE Campbell H Esko T Wilson JF Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan Nat Commun 2016 7 11174 https://doi.org/10.1038/ncomms11174 27029810 PMC5438072 · DOI
  14. [14]Welter D MacArthur J Morales J Burdett T Hall P Junkins H Klemm A Flicek P Manolio T Hindorff L Parkinson H The NHGRI GWAS Catalog, a curated resource of SNP-trait associations Nucleic Acids Res 2014 42 D1001 06 https://doi.org/10.1093/nar/gkt1229 24316577 PMC3965119 · DOI · Paper page
  15. [15]Zhernakova DV Deelen P Vermaat M van Iterson M van Galen M Arindrarto W van't Hof P Mei H van Dijk F Westra HJ Bonder MJ van Rooij J Verkerk M Identification of context-dependent expression quantitative trait loci in whole blood Nat Genet 2017 49 139 45 https://doi.org/10.1038/ng.3737 27918533 · DOI · Paper page
  16. [16]Watanabe K Taskesen E van Bochoven A Posthuma D FUMA: functional mapping and annotation of genetic associations bioRxiv 2017 110023 https://doi.org/10.1101/110023 PMC5705698 29184056 · DOI
  17. [17]Locke AE Kahali B Berndt SI Justice AE Pers TH Day FR Powell C Vedantam S Buchkovich ML Yang J Croteau-Chonka DC Esko T Fall T LifeLines Cohort Study, and ADIPOGen Consortium, and AGEN-BMI Working Group, and CARDIOGRAMplusC4D Consortium, and CKDGen Consortium, and GLGC, and ICBP, and MAGIC Investigators, and MuTHER Consortium, and MIGen Consortium, and PAGE Consortium, and ReproGen Consortium, and GENIE Consortium, and International Endogene Consortium Genetic studies of body mass index yield new insights for obesity biology Nature 2015 518 197 206 https://doi.org/10.1038/nature14177 25673413 PMC4382211 · DOI · Paper page
  18. [18]Michailidou K Beesley J Lindstrom S Canisius S Dennis J Lush MJ Maranian MJ Bolla MK Wang Q Shah M Perkins BJ Czene K Eriksson M BOCS, and kConFab Investigators, and AOCS Group, and NBCS, and GENICA Network Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer Nat Genet 2015 47 373 80 https://doi.org/10.1038/ng.3242 25751625 PMC4549775 · DOI
  19. [19]Okbay A Beauchamp JP Fontana MA Lee JJ Pers TH Rietveld CA Turley P Chen GB Emilsson V Meddens SF Oskarsson S Pickrell JK Thom K LifeLines Cohort Study Genome-wide association study identifies 74 loci associated with educational attainment Nature 2016 533 539 42 https://doi.org/10.1038/nature17671 27225129 PMC4883595 · DOI · Paper page
  20. [20]Pattaro C Teumer A Gorski M Chu AY Li M Mijatovic V Garnaas M Tin A Sorice R Li Y Taliun D Olden M Foster M ICBP Consortium, and AGEN Consortium, and CARDIOGRAM, and CHARGe-Heart Failure Group, and ECHOGen Consortium Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function Nat Commun 2016 7 10023 https://doi.org/10.1038/ncomms10023 26831199 PMC4735748 · DOI
  21. [22]Aguilo F Di Cecilia S Walsh MJ Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease Curr Top Microbiol Immunol 2016 394 29 39 https://doi.org/10.1007/82_2015_455 26220772 PMC4732918 · DOI
  22. [24]Bochenek G Häsler R El Mokhtari NE König IR Loos BG Jepsen S Rosenstiel P Schreiber S Schaefer AS The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10 Hum Mol Genet 2013 22 4516 27 https://doi.org/10.1093/hmg/ddt299 23813974 · DOI
  23. [25]Congrains A Kamide K Oguro R Yasuda O Miyata K Yamamoto E Kawai T Kusunoki H Yamamoto H Takeya Y Yamamoto K Onishi M Sugimoto K Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B Atherosclerosis 2012 220 449 55 https://doi.org/10.1016/j.atherosclerosis.2011.11.017 22178423 · DOI
  24. [26]Dale BL Madhur MS Linking inflammation and hypertension via LNK/SH2B3 Curr Opin Nephrol Hypertens 2016 25 87 93 https://doi.org/10.1097/MNH.0000000000000196 26717315 PMC4763980 · DOI
  25. [27]Sato K Emi M Ezura Y Fujita Y Takada D Ishigami T Umemura S Xin Y Wu LL Larrinaga-Shum S Stephenson SH Hunt SC Hopkins PN Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred J Hum Genet 2004 49 29 34 https://doi.org/10.1007/s10038-003-0103-6 14673705 · DOI
  26. [28]Wei Q Doris PA Pollizotto MV Boerwinkle E Jacobs DR Jr Siscovick DS Fornage M Sequence variation in the soluble epoxide hydrolase gene and subclinical coronary atherosclerosis: interaction with cigarette smoking Atherosclerosis 2007 190 26 34 https://doi.org/10.1016/j.atherosclerosis.2006.02.021 16545818 · DOI
  27. [29]Barrell D Dimmer E Huntley RP Binns D O'Donovan C Apweiler R The GOA database in 2009—an integrated Gene Ontology Annotation resource Nucleic Acids Res 2009 37 D396 403 https://doi.org/10.1093/nar/gkn803 18957448 PMC2686469 · DOI
  28. [30]Pesu M Watford WT Wei L Xu L Fuss I Strober W Andersson J Shevach EM Quezado M Bouladoux N Roebroek A Belkaid Y Creemers J O'Shea JJ T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance Nature 2008 455 246 50 https://doi.org/10.1038/nature07210 18701887 PMC2758057 · DOI
  29. [32]Meimaridou E Hughes CR Kowalczyk J Chan LF Clark AJ Metherell LA ACTH resistance: genes and mechanisms Endocr Dev 2013 24 57 66 https://doi.org/10.1159/000342504 23392095 · DOI
  30. [33]Fry A Littlejohns TJ Sudlow C Doherty N Adamska L Sprosen T Collins R Allen NE Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population Am J Epidemiol 2017 186 1026 34 https://doi.org/10.1093/aje/kwx246 28641372 PMC5860371 · DOI · Paper page
  31. [34]Sebastiani P Bae H Gurinovich A Soerensen M Puca A Perls TT Limitations and risks of meta-analyses of longevity studies Mech Ageing Dev 2017 165 139 46 https://doi.org/10.1016/j.mad.2017.01.008 28143747 PMC5533653 · DOI
  32. [35]Locke JM Hysenaj G Wood AR Weedon MN Harries LW Targeted allelic expression profiling in human islets identifies cis-regulatory effects for multiple variants identified by type 2 diabetes genome-wide association studies Diabetes 2015 64 1484 91 https://doi.org/10.2337/db14-0957 25392243 · DOI
  33. [37]Bycroft C Freeman C Petkova D Band G Elliott LT Sharp K Motyer A Vukcevic D Delaneau O O'Connell J Cortes A Welsh S McVean G Genome-wide genetic data on ∼500,000 UK Biobank participants bioRxiv 2017 https://doi.org/10.1101/166298 · DOI
  34. [38]Loh PR Tucker G Bulik-Sullivan BK Vilhjálmsson BJ Finucane HK Salem RM Chasman DI Ridker PM Neale BM Berger B Patterson N Price AL Efficient Bayesian mixed-model analysis increases association power in large cohorts Nat Genet 2015 47 284 90 https://doi.org/10.1038/ng.3190 25642633 PMC4342297 · DOI · Paper page
  35. [39]Purcell S Neale B Todd-Brown K Thomas L Ferreira MA Bender D Maller J Sklar P de Bakker PI Daly MJ Sham PC PLINK: a tool set for whole-genome association and population-based linkage analyses Am J Hum Genet 2007 81 559 75 https://doi.org/10.1086/519795 17701901 PMC1950838 · DOI · Paper page
  36. [41]Astle WJ Elding H Jiang T Allen D Ruklisa D Mann AL Mead D Bouman H Riveros-Mckay F Kostadima MA Lambourne JJ Sivapalaratnam S Downes K The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease Cell 2016 167 1415 1429.e19 https://doi.org/10.1016/j.cell.2016.10.042 27863252 PMC5300907 · DOI · Paper page
  37. [43]Wood AR Esko T Yang J Vedantam S Pers TH Gustafsson S Chu AY Estrada K Luan J Kutalik Z Amin N Buchkovich ML Croteau-Chonka DC Electronic Medical Records and Genomics (eMEMERGEGE) Consortium, and MIGen Consortium, and PAGEGE Consortium, and LifeLines Cohort Study Defining the role of common variation in the genomic and biological architecture of adult human height Nat Genet 2014 46 1173 86 https://doi.org/10.1038/ng.3097 25282103 PMC4250049 · DOI · Paper page
  38. [44]Ehret GB Munroe PB Rice KM Bochud M Johnson AD Chasman DI Smith AV Tobin MD Verwoert GC Hwang SJ Pihur V Vollenweider P O'Reilly PF CHARGE-HF consortium Genetic variants in novel pathways influence blood pressure and cardio-vascular disease risk Nature 2011 478 103 09 https://doi.org/10.1038/nature10405 21909115 PMC3340926 · DOI · Paper page
  39. [45]Willer CJ Schmidt EM Sengupta S Peloso GM Gustafsson S Kanoni S Ganna A Chen J Buchkovich ML Mora S Beckmann JS Bragg-Gresham JL Chang HY Global Lipids Genetics Consortium Discovery and refinement of loci associated with lipid levels Nat Genet 2013 45 1274 83 https://doi.org/10.1038/ng.2797 24097068 PMC3838666 · DOI

Cited by

Sorted by citations

Authors
Pilling, L. C., Kuo, C.-L., Sicinski, K., Tamosauskaite, J., Kuchel, G. A., Harries, L. W., Herd, P., Wallace, R., Ferrucci, L., & Melzer, D.
Affiliations
  • University of Exeter (GB)
  • UConn Health (US)
  • University of Wisconsin–Madison (US)
  • University of Connecticut (US)
  • University of Iowa (US)
  • National Institute on Aging (US)
Corresponding author
Melzer, David
ORCID
Venue
Aging
Publisher
Impact Journals, LLC
Published
2017-12-06
Volume
9
Issue
12
Pages
2504-2520
ISSN
1945-4589 (ISSN-L)
DOI
10.18632/aging.101334
PMC
PMC5764389
OpenAlex
W2771230199
Cited by
211
References
5
Citations by year
2026: 16 · 2025: 27 · 2024: 24 · 2023: 19 · 2022: 31 · 2021: 16 · 2020: 35 · 2019: 26 · 2018: 17
FWCI
14.70
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion)
  • Open Research Exeter (University of Exeter) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (5p01ag021079-08)
  • Medical Research Council (MR/M023095/1)
  • National Institute on Aging (R01AG033285, P01-AG021079, R01AG009775, U01AG009740, P30AG017266)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords
human longevity, genetic loci, polygenic risk, cellular senescence, inflammation, lipid metabolism, cardiovascular disease, sex differences
MeSH terms
Adult, Aged, Female, United Kingdom, Humans, Longevity, Male, Middle Aged, Parents, Biological Specimen Banks, Multifactorial Inheritance, Genome-Wide Association Study

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review