Evidence map›Paper›PMID 27329260›Full record

SynthesisAging cell2016

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits.

Alexander Teumer, Qibin Qi, Maria Nethander, Hugues Aschard, Stefania Bandinelli, Marian Beekman, Sonja I Berndt, Martin Bidlingmaier, Linda Broer, CHARGE Longevity Working Group and 78 more

Erratum issuedOpen access · goldAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Aging cell, 2016. 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 52 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 2 pooled it
10.9field-weighted citation impact, top 1% of its field
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

52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. FoxO3 and oxidative stress: a multifaceted role in cellular adaptation.Journal of molecular medicine (Berlin, Germany) · 2023
    Review
  10. Article
  11. Review
  12. Genes · 2022
    Article
  13. Article
  14. Review
  15. Investigation of the Interplay between Circulating Lipids and IGF-I and Relevance to Breast Cancer Risk: An Observational and Mendelian Randomization Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021
    Observational
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

88 authors at 20 institutions in 12 countries.

Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, 17475, Greifswald, Germany.
Qibin QiDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Maria NethanderBioinformatics Core Facility, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden.
Hugues AschardProgram in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA.
Stefania BandinelliGeriatric Unit, Azienda Sanitaria di Firenze (ASF), Florence, Italy.
Marian BeekmanMolecular Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20892, USA.
Martin BidlingmaierMedizinische Klinik und Poliklinik IV, Klinikum der Universitaet Muenchen, 80336, Munich, Germany.
Linda BroerDepartment of Epidemiology, Subdivision Genetic Epidemiology, Erasmus Medical Center, Postbus 2040, 3000 CA, Rotterdam, The Netherlands.
CHARGE Longevity Working Group
Anne CappolaDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA.
Gian Paolo CedaSection of Geriatrics, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
Stephen ChanockInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475, Greifswald, Germany.
Ming-Huei ChenFramingham Heart Study, Framingham, MA, 01702, USA.
Tai C ChenSection of Endocrinology, Diabetes & Nutrition, Boston University School of Medicine, Boston, MA, 02118, USA.
Yii-Der Ida ChenInstitute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
Jonathan ChungDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Fabiola Del Greco MiglianicoCenter for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, 39100, Italy.
Joel ErikssonDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden.
Luigi FerrucciTranslational Gerontology Branch, National Institute on Aging, Baltimore, MD, 21225, USA.
Nele FriedrichInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475, Greifswald, Germany.
Carsten GnewuchInstitute for Clinical Chemistry and Laboratory Medicine, Regensburg University Medical Center, D-93053, Regensburg, Germany.
Mark O GoodarziDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Niels GrarupThe Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Tingwei GuoDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Elke HammerInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475, Greifswald, Germany.
Richard B HayesDivision of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, 10016, USA.
Andrew A HicksCenter for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, 39100, Italy.
Albert HofmanDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands.
Jeanine J Houwing-DuistermaatLeiden University Medical Center, Medical Statistics and Bioinformatics, Leiden, 2300 RC, The Netherlands.
Frank HuDepartment of Nutrition, Harvard School of Public Health, Boston, MA, 02115, USA.
David J HunterDepartment of Nutrition, Harvard School of Public Health, Boston, MA, 02115, USA.
Lise L HusemoenResearch Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, DK-2600, Denmark.
Aaron IsaacsGenetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherland.
Kevin B JacobsInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475, Greifswald, Germany.
Joop A M J L JanssenDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands.
John-Olov JanssonDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden.
Nico JehmlichInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475, Greifswald, Germany.
Simon JohnsonDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Anders JuulDepartment of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, DK-2100, Denmark.
Magnus KarlssonClinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, 20502, Malmö, Sweden.
Tuomas O KilpelainenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Peter KovacsIFB Adiposity Diseases, University of Leipzig, 04103, Leipzig, Germany.
Peter KraftChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Chao LiDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Allan LinnebergResearch Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, DK-2600, Denmark.
Yongmei LiuDivision of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Ruth J F LoosThe Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Body Composition Genetics Consortium
Mattias LorentzonDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden.
Yingchang LuThe Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Marcello MaggioSection of Geriatrics, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
Reedik MagiEstonian Genome Center, University of Tartu, Tartu, Estonia.
James MeigsGeneral Medicine Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Dan MellströmDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden.
Matthias NauckDepartment of Nutrition, Harvard School of Public Health, Boston, MA, 02115, USA.
Anne B NewmanDepartment of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Michael N PollakDepartments of Experimental Medicine and Oncology, McGill University, Montréal, Québec, Canada, H3A 0G4.
Peter P PramstallerCenter for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, 39100, Italy.
Inga ProkopenkoDepartment of Genomics of Common Disease, School of Public Health, Imperial College London, London, W12ONN, UK.
Bruce M PsatyDepartments of Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, 98101, USA.
Martin ReinckeMedizinische Klinik und Poliklinik IV, Klinikum der Universitaet Muenchen, 80336, Munich, Germany.
Eric B RimmDepartment of Nutrition, Harvard School of Public Health, Boston, MA, 02115, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
Aude Saint PierreINSERM U1078, Brest, France.
Claudia SchurmannThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Sudha SeshadriFramingham Heart Study, Framingham, MA, 01702, USA.
Klara SjögrenDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden.
P Eline SlagboomMolecular Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
Howard D StricklerDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Michael StumvollIFB Adiposity Diseases, University of Leipzig, 04103, Leipzig, Germany.
Yousin SuhDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Qi SunDepartment of Nutrition, Harvard School of Public Health, Boston, MA, 02115, USA.
Cuilin ZhangEpidemiology Branch, Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Blvd, Rockville, MD, 20852, USA.
Johan SvenssonDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden.
Toshiko TanakaTranslational Gerontology Branch, National Institute on Aging, Baltimore, MD, 21225, USA.
Archana TareDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Anke TönjesMedical Department, University of Leipzig, 04103, Leipzig, Germany.
Hae-Won UhLeiden University Medical Center, Medical Statistics and Bioinformatics, Leiden, 2300 RC, The Netherlands.
Cornelia M van DuijnGenetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherland.
Diana van HeemstGerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
Liesbeth VandenputDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden.
Ramachandran S VasanBoston University and National Heart, Lung & Blood Institute's Framingham Heart Study, Framingham, MA, 01702, USA.
Uwe VölkerInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475, Greifswald, Germany.
Sara M WillemsGenetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherland.
Claes OhlssonDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden.
Henri WallaschofskiInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475, Greifswald, Germany.
Robert C KaplanDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Albert Einstein College of Medicine · USBrigham and Women's Hospital · USUniversitätsmedizin Greifswald · DEBoston University · USLeiden University Medical Center · NLEurac Research · ITUniversity of Copenhagen · DKUniversity of Parma · ITErasmus MC · NLHarvard University · USInserm · FRMassachusetts Department of Public Health · USNational Institute on Aging · USUniversity of Gothenburg · SEUniversity of Washington · USAzienda Sanitaria di Firenze · ITCedars-Sinai Medical Center · USCentre for Human Genetics · GBCentre for Medical Systems Biology · NLChild Health and Development Institute · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
THE IMPACT OF CELLULAR DEFENSE ON THE ROLE OF Ku80 IN GENOME MAINTENANCE AND LONGP01AG017242 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI VIJG, JAN · 1999 to 2023
$46.1M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
VARIABILITY, STABILITY & SMOOTHNESS OF WALKINGP30AG024827 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Caterina Rosano · 2004 to 2026
$28.6M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
Common Genetic Variation and Quantitative Diabetes TraitsR01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2008 to 2014
$5.0M
Rare Sequence Variation and Diabetes Quantitative TraitsU01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2015 to 2019
$3.6M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS R01 HL075516NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS U01 HL120393NIA NIH HHS P01 AG017242NIA NIH HHS P30 AG024827NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG031890NIDDK NIH HHS K24 DK080140NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK078616NIDDK NIH HHS U01 DK078616
6 · The paper itself

Abstract

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci.

Indexed as

Genome-Wide Association StudyQuantitative Trait, HeritableAdultAgingFemaleGene Expression RegulationHumansInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor IMaleMetabolomeQuantitative Trait LociRegulatory Sequences, Nucleic AcidInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor Iaginggenomewide association studygrowth hormone axisIGFBP-3IGF-Ilongevity

Identifiers

PMID27329260
PMCPMC5013013
OpenAlexW2461170015

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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.