Evidence map›Paper›PMID 25199915›Full record

SynthesisThe journals of gerontology. Series A, Biological sciences and medical sciences2015

GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.

Linda Broer, Aron S Buchman, Joris Deelen, Daniel S Evans, Jessica D Faul, Kathryn L Lunetta, Paola Sebastiani, Jennifer A Smith, Albert V Smith, Toshiko Tanaka and 37 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The journals of gerontology. Series A, Biological sciences and medical sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 13 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

182 citing papers in PubMed, 13 syntheses or guidelines pooled it.

  1. Pooled it
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  5. APOE Alleles and Extreme Human Longevity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2019
    Pooled it
  6. Effects of FOXO3 Polymorphisms on Survival to Extreme Longevity in Four Centenarian Studies.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018
    Pooled it
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  9. Limitations and risks of meta-analyses of longevity studies.Mechanisms of ageing and development · 2017
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122 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

47 authors.

Linda BroerDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, The Netherlands. Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Aron S BuchmanRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.
Joris DeelenNetherlands Consortium for Healthy Ageing, Leiden University Medical Center, The Netherlands. Department of Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
Daniel S EvansCalifornia Pacific Medical Center Research Institute, San Francisco.
Jessica D FaulSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor.
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Massachusetts. NHLBI's and Boston Univesity's Framingham Heart Study, Massachusetts.
Paola SebastianiDepartment of Biostatistics, Boston University School of Public Health, Massachusetts.
Jennifer A SmithDepartment of Epidemiology, University of Michigan, Ann Arbor.
Albert V SmithIcelandic Heart Association, Kopavogur, Iceland. Department of Medicine, University of Iceland, Reykjavik.
Toshiko TanakaTranslational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
Lei YuRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.
Alice M ArnoldDepartment of Biostatistics, University of Washington, Seattle.
Thor AspelundIcelandic Heart Association, Kopavogur, Iceland. Department of Medicine, University of Iceland, Reykjavik.
Emelia J BenjaminNHLBI's and Boston Univesity's Framingham Heart Study, Massachusetts. Department of Medicine, Sections of Preventive Medicine and Cardiology, Boston University School of Medicine, Massachusetts. Department of Epidemiology, Boston University School of Public Health, Massachusetts.
Philip L De JagerProgram in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Gudny EirkisdottirIcelandic Heart Association, Kopavogur, Iceland.
Denis A EvansRush Institute for Healthy Aging and Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois.
Melissa E GarciaLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland.
Albert HofmanDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, The Netherlands.
Robert C KaplanDepartment of Epidemiology and Population Health, Albert Einstein College, Bronx, New York.
Sharon L R KardiaDepartment of Epidemiology, University of Michigan, Ann Arbor.
Douglas P KielHarvard Medical School, Boston, Massachusetts. Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School Department of Medicine, Boston, Massachusetts. Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Ben A OostraDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, The Netherlands.
Eric S OrwollSchool of Medicine, Oregon Health and Science University, Portland.
Neeta ParimiCalifornia Pacific Medical Center Research Institute, San Francisco.
Bruce M PsatyDepartment of Medicine, University of Washington, Seattle. Deparment of Epidemiology, University of Washington, Seattle. Department of Health Services, University of Washington, Seattle. Group Health Research Institute, Group Health Cooperative, Seattle, Washington.
Fernando RivadeneiraDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School Department of Medicine, Boston, Massachusetts.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California.
Sudha SeshadriDepartment of Biostatistics, Boston University School of Public Health, Massachusetts. Department of Neurology, Boston University School of Medicine, Massachusetts.
Andrew SingletonLaboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
Henning TiemeierDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, The Netherlands. Department of Child and Adolescent Psychiatry, Erasmus MC and Sophia Children's Hospital, Rotterdam, The Netherlands.
André G UitterlindenDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, The Netherlands. Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Wei ZhaoDepartment of Epidemiology, University of Michigan, Ann Arbor.
Stefania BandinelliGeriatric Unit, Azienda Sanitaria Firenze, Florence, Italy.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.
Luigi FerrucciTranslational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
Vilmundur GudnasonIcelandic Heart Association, Kopavogur, Iceland. Department of Medicine, University of Iceland, Reykjavik.
Tamara B HarrisLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland.
David KarasikInstitute for Aging Research, Hebrew SeniorLife, Harvard Medical School Department of Medicine, Boston, Massachusetts. Faculty of Medicine in The Galilee, Bar-Ilan University, Safed, Israel.
Lenore J LaunerLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland.
Thomas T PerlsSection of Geriatrics, Boston University School of Medicine and Boston Medical Center, Massachusetts.
P Eline SlagboomNetherlands Consortium for Healthy Ageing, Leiden University Medical Center, The Netherlands. Department of Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
Gregory J TranahCalifornia Pacific Medical Center Research Institute, San Francisco. Department of Epidemiology and Biostatistics, University of California, San Francisco.
David R WeirSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor.
Anne B NewmanDepartment of Epidemiology, University of Pittsburgh, Pennsylvania. *These authors contributed equally to this work.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, The Netherlands. *These authors contributed equally to this work.
Joanne M MurabitoNHLBI's and Boston Univesity's Framingham Heart Study, Massachusetts. Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine, Massachusetts. *These authors contributed equally to this work. murabito@bu.edu.

Funding

HRS Yrs29-34: Y33 SSA CoFundingU01AG009740 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jessica Faul, KENNETH M LANGA · 1990 to 2026
$555.8M
Systems BiologyU19AG023122 · NIA · TRANSLATIONAL GENOMICS RESEARCH INST · PI FRED H GAGE · 2004 to 2026
$102.6M
OREGON CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024140 · NCRR · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2006 to 2011
$61.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Risk Factors for Incident Alzheimer's Disease in a Biracial CommunityR01AG011101 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI EVANS, DENIS A · 1993 to 2010
$24.7M
Study of Osteoporotic FracturesR01AG005407 · NIA · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI CUMMINGS, STEVEN RON, YAFFE, KRISTINE · 1986 to 2016
$23.2M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
CCR NIH HHS RC2ARO58973NCATS NIH HHS UL1TR000124NCRR NIH HHS UL1 RR024140NHLBI NIH HHS 1R01HL092577NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HL080295NHLBI NIH HHS HL087652NHLBI NIH HHS HL105756NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS N01HC55222NHLBI NIH HHS N01HC85079NHLBI NIH HHS N01HC85080NHLBI NIH HHS N01HC85081NHLBI NIH HHS N01HC85082NHLBI NIH HHS N01HC85083NHLBI NIH HHS N01HC85086NHLBI NIH HHS N02-HL-6-4278NIAMS NIH HHS R01-AR051124NIAMS NIH HHS R01 AR35582NIAMS NIH HHS R01 AR35583NIAMS NIH HHS R01 AR35584NIAMS NIH HHS U01 AR45580NIAMS NIH HHS U01 AR45583NIAMS NIH HHS U01 AR45614NIAMS NIH HHS U01 AR45632NIAMS NIH HHS U01 AR45647NIAMS NIH HHS U01 AR45654NIA NIH HHS 1R01AG028321NIA NIH HHS AG023629NIA NIH HHS N01-AG-12100NIA NIH HHS P30AG10161NIA NIH HHS R01 AG005394NIA NIH HHS R01 AG027574NIA NIH HHS R01 AG027576NIA NIH HHS R01AG15819NIA NIH HHS R01AG17917NIA NIH HHS R01AG29451NIA NIH HHS R01AG30146NIA NIH HHS R01 AR/AG 41398NIA NIH HHS RC2 AG036495NIA NIH HHS RC4 AG039029NIA NIH HHS U01AG009740NIA NIH HHS U01-AG023755NIA NIH HHS U01-AG027810NIA NIH HHS U01 AG18197NIA NIH HHS U19-AG023122NIDDK NIH HHS DK063491NIMHD NIH HHS 263 MD 821336NIMHD NIH HHS 263 MD 9164
6 · The paper itself

Abstract

backgroundThe genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.

methodsWe conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.

resultsIn our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)).

conclusionsWe did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

Indexed as

AgedAged, 80 and overApolipoproteins ECell Adhesion MoleculesCohort StudiesFemaleForkhead Box Protein O3Forkhead Transcription FactorsGenome-Wide Association StudyGluK2 Kainate ReceptorHumansKainic Acid ReceptorsLongevityMaleMiddle AgedPolymorphism, Single NucleotideApolipoproteins ECADM2 protein, humanCell Adhesion MoleculesForkhead Box Protein O3Forkhead Transcription FactorsFOXO3 protein, humanGluK2 Kainate ReceptorKainic Acid ReceptorsAPOE.FOXO3GWASLongevity

Identifiers

PMID25199915
PMCPMC4296168

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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.