Evidence map›Paper›PMID 34187551›Full record

ArticleGenome biology2021

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

Daniel L McCartney, Josine L Min, Rebecca C Richmond, Ake T Lu, Maria K Sobczyk, Gail Davies, Linda Broer, Xiuqing Guo, Ayoung Jeong, Jeesun Jung and 101 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
195citing papers in PubMed, 11 pooled it
16.3field-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

195 citing papers in PubMed, 11 syntheses or guidelines pooled it, 290 citations in OpenAlex.

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  9. The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022
    Pooled it
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  15. Evolutionary genetics of ageing.Nature reviews. Genetics · 2026
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135 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

111 authors at 20 institutions in 14 countries.

Daniel L McCartney *Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK.
Josine L Min *MRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
Rebecca C Richmond *MRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
Ake T Lu *Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Maria K Sobczyk *MRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
Gail Davies *Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Linda Broer *Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
Xiuqing Guo *The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Ayoung Jeong *Swiss Tropical and Public Health Institute, Basel, Switzerland.
Jeesun Jung *National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, USA.
Silva Kasela *Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Seyma Katrinli *Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
Pei-Lun Kuo *Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Pamela R Matias-Garcia *Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
Pashupati P Mishra *Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, 33520, Tampere, Finland.
Marianne Nygaard *Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Teemu Palviainen *Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Amit Patki *Department of Biostatistics, University of Alabama at Birmingham, Birmingham, USA.
Laura M Raffield *Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Scott M Ratliff *Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
Tom G Richardson *MRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
Oliver Robinson *MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Mette Soerensen *Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Dianjianyi Sun *Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
Pei-Chien Tsai *Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Matthijs D van der Zee *Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Rosie M Walker *Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK.
Xiaochuan Wang *Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria, 3004, Australia.
Yunzhang Wang *Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Rui Xia *Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Zongli Xu *National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
Jie Yao *The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Wei Zhao *Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
Adolfo CorreaDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Eric BoerwinkleSchool of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Pierre-Antoine DuguéCancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria, 3004, Australia.
Peter DurdaDepartment of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05446, USA.
Hannah R ElliottMRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
Christian GiegerResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
Genetics of DNA Methylation Consortium
Eco J C de GeusDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Sarah E HarrisLothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Gibran HemaniMRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
Medea ImbodenSwiss Tropical and Public Health Institute, Basel, Switzerland.
Mika KähönenDepartment of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, 33521, Tampere, Finland.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
Jacob K KresovichNational Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
Shengxu LiChildren's Minnesota Research Institute, Children's Minnesota, Minneapolis, MN, 55404, USA.
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, USA.
Massimo ManginoDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Dan MasonBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
Andrew M McIntoshDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.
Jonas Mengel-FromEpidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Ann Zenobia MooreLongitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Joanne M MurabitoSection of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Miina OllikainenInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
James S PankowDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
Nancy L PedersenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Annette PetersInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
Silvia PolidoroMRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
David J PorteousCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK.
Olli RaitakariCentre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
Stephen S RichDepartment of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
Dale P SandlerNational Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
Elina SillanpääInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Alicia K SmithDepartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
Melissa C SoutheyCancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria, 3004, Australia.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
Hemant TiwariDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, USA.
Toshiko TanakaLongitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Therese TillinMRC Unit for Lifelong Health and Ageing at UCL, London, UK.
Andre G UitterlindenDepartment of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
David J Van Den BergCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Jenny van DongenDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
James G WilsonDivision of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
John WrightBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
Idil YetDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Donna ArnettDeans Office, College of Public Health, University of Kentucky, Lexington, UK.
Stefania BandinelliGeriatric Unit, Azienda Sanitaria Toscana Centro, Florence, Italy.
Jordana T BellDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Alexandra M BinderDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
Dorret I BoomsmaDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Wei ChenDepartment of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
Kaare ChristensenEpidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Karen N ConneelyDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Paul ElliottMRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Luigi FerrucciLongitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Myriam FornageBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Sara HäggDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Caroline HaywardMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Crewe Rd. South, Edinburgh, EH4 2XU, UK.
Marguerite IrvinDept of Epidemiology, University of Alabama at Birmingham, Birmingham, USA.
Jaakko KaprioInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Deborah A LawlorMRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, 33520, Tampere, Finland.
Falk W LohoffNational Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, USA.
Lili MilaniEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Roger L MilneCancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria, 3004, Australia.
Nicole Probst-HenschSwiss Tropical and Public Health Institute, Basel, Switzerland.
Alex P ReinerDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
Beate RitzDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
Jack A TaylorNational Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
Joyce B J van MeursDepartment of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
Paolo VineisMRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Melanie WaldenbergerResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
Ian J DearyLothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Caroline L ReltonMRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
Steve Horvath *Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.
Riccardo E Marioni *Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK. riccardo.marioni@ed.ac.uk.ORCID 0000-0003-4430-4260
University of Bristol · GBEdinburgh Cancer Research · GBHelmholtz Zentrum München · DEMRC Centre for Environment and HealthNational Institute on Aging · USTriangle · USUniversity of Edinburgh · GBUniversity of Helsinki · FIUniversity of Michigan · USUniversity of Southern Denmark · DKVrije Universiteit Amsterdam · NLEmory University · USErasmus MC · NLKarolinska Institutet · SEKing's College London · GBSwiss Tropical and Public Health Institute · CHThe University of Melbourne · AUUCLA Medical Center · USUniversity of Alabama at Birmingham · USUniversity of California, Los Angeles · US

Funding

Clinical Genomics and Experimental TherapeuticsZIAAA000242 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI LOHOFF, FALK · 2015 to 2025
$26.7M
Environmental and Genetic Risk Factors For Breast Cancer: The Sister StudyZIAES044005 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI SANDLER, DALE P · 2009 to 2025
$22.7M
Environmental Exposure and DNA DamageZIAES049032 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI TAYLOR, JACK A · 2009 to 2022
$13.4M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
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
The Aging Genome Association Study "AGE-GAIN"ZIAAG000965 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2025
$4.0M
Validation and optimization of epigenetic clocksU01AG060908 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2018 to 2022
$3.4M
A Social Epigenomic Approach to Health Disparities in Cardiovascular Risk FactorsR01HL141292 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SMITH, JENNIFER ANN · 2018 to 2021
$2.9M
Evaluating Longitudinal Changes in the Human Structural Connectome in Relation to Cognitive AgingR01AG054628 · NIA · UNIVERSITY OF TEXAS AT AUSTIN · PI TUCKER-DROB, ELLIOT MAX · 2017 to 2021
$2.7M
Epigenetics of Arteriosclerosis in African American Hypertensive SibshipsR01HL133221 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SMITH, JENNIFER ANN · 2016 to 2019
$2.2M
The InChianti StudyZIAAG001050 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2025
$2.1M
Biotechnology and Biological Sciences Research Council BB/S020845/1Cancer Research UK 29019Cancer Research UK C18281/A191169Medical Research Council MC_UU_00007/10Medical Research Council MC_UU_00011/5Medical Research Council MC_UU_00011/6Medical Research Council MR/R023484/1Medical Research Council MR/R0245065/1Medical Research Council MR/S03532X/1NHLBI NIH HHS HHSN268201000001INHLBI NIH HHS HHSN268201000021CNHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL133221NHLBI NIH HHS R01 HL141292NHLBI NIH HHS U01 HL120393NIA NIH HHS R01 AG054628NIA NIH HHS U01 AG060908Wellcome Trust 208806/Z/17/Z
6 · The paper itself

Abstract

backgroundBiological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.

resultsLeveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.

conclusionThis study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

Indexed as

DNA MethylationEpigenesis, GeneticGenetic LociMultifactorial InheritanceAdiposityAgingBiomarkersCpG IslandsC-Reactive ProteinEducational StatusGenetic MarkersGenome, HumanGenome-Wide Association StudyGranulocytesHumansImmunity, InnateBiomarkersC-Reactive ProteinGenetic MarkersPlasminogen Activator Inhibitor 1SERPINE1 protein, humanDNA methylationEpigenetic clockGWAS

Identifiers

PMID34187551
PMCPMC8243879
OpenAlexW3177165321

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.