. 2021 Jun 29;22(1):194.

doi: 10.1186/s13059-021-02398-9.

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

Daniel L McCartney^#¹, Josine L Min^#^{2

3}, Rebecca C Richmond^#^{2

3}, Ake T Lu^#⁴, Maria K Sobczyk^#^{2

3}, Gail Davies^#⁵, Linda Broer^#⁶, Xiuqing Guo^#⁷, Ayoung Jeong^#^{8

9}, Jeesun Jung^#¹⁰, Silva Kasela^#¹¹, Seyma Katrinli^#¹², Pei-Lun Kuo^#¹³, Pamela R Matias-Garcia^#^{14

15

16}, Pashupati P Mishra^#¹⁷, Marianne Nygaard^#^{18

19}, Teemu Palviainen^#²⁰, Amit Patki^#²¹, Laura M Raffield^#²², Scott M Ratliff^#²³, Tom G Richardson^#^{2

3}, Oliver Robinson^#²⁴, Mette Soerensen^#^{18

19

25}, Dianjianyi Sun^#²⁶, Pei-Chien Tsai^#^{27

28

29}, Matthijs D van der Zee^#^{30

31}, Rosie M Walker^#¹, Xiaochuan Wang^#³², Yunzhang Wang^#³³, Rui Xia^#³⁴, Zongli Xu^#³⁵, Jie Yao^#⁷, Wei Zhao^#²³, Adolfo Correa³⁶, Eric Boerwinkle³⁷, Pierre-Antoine Dugué^{32

38

39}, Peter Durda⁴⁰, Hannah R Elliott^{2

3}, Christian Gieger^{14

15}; Genetics of DNA Methylation Consortium; Eco J C de Geus^{30

31}, Sarah E Harris⁵, Gibran Hemani^{2

3}, Medea Imboden^{8

9}, Mika Kähönen⁴¹, Sharon L R Kardia²³, Jacob K Kresovich³⁵, Shengxu Li⁴², Kathryn L Lunetta⁴³, Massimo Mangino^{27

44}, Dan Mason⁴⁵, Andrew M McIntosh⁴⁶, Jonas Mengel-From^{18

19}, Ann Zenobia Moore¹³, Joanne M Murabito⁴⁷; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; Miina Ollikainen²⁰, James S Pankow⁴⁸, Nancy L Pedersen³³, Annette Peters^{15

49}, Silvia Polidoro²⁴, David J Porteous¹, Olli Raitakari^{50

51

52}, Stephen S Rich⁵³, Dale P Sandler³⁵, Elina Sillanpää^{20

54}, Alicia K Smith^{12

55}, Melissa C Southey^{32

38

39}, Konstantin Strauch^{56

57

58}, Hemant Tiwari²¹, Toshiko Tanaka¹³, Therese Tillin⁵⁹, Andre G Uitterlinden^{6

60}, David J Van Den Berg⁶¹, Jenny van Dongen^{30

31}, James G Wilson^{62

63}, John Wright⁴⁵, Idil Yet^{27

64}, Donna Arnett⁶⁵, Stefania Bandinelli⁶⁶, Jordana T Bell²⁷, Alexandra M Binder^{67

68}, Dorret I Boomsma^{30

31}, Wei Chen⁶⁹, Kaare Christensen^{18

19

25}, Karen N Conneely⁷⁰, Paul Elliott²⁴, Luigi Ferrucci¹³, Myriam Fornage³⁴, Sara Hägg³³, Caroline Hayward⁷¹, Marguerite Irvin⁷², Jaakko Kaprio^{20

73}, Deborah A Lawlor^{2

3

74}, Terho Lehtimäki¹⁷, Falk W Lohoff¹⁰, Lili Milani¹¹, Roger L Milne^{32

38

39}, Nicole Probst-Hensch^{8

9}, Alex P Reiner⁷⁵, Beate Ritz⁶⁷, Jerome I Rotter⁷, Jennifer A Smith²³, Jack A Taylor³⁵, Joyce B J van Meurs^{6

60}, Paolo Vineis²⁴, Melanie Waldenberger^{14

15

49}, Ian J Deary⁵, Caroline L Relton^{2

3}, Steve Horvath^#^{76

77}, Riccardo E Marioni^#⁷⁸

Affiliations

¹ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK.
² MRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
³ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁴ Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁵ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁶ Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
⁷ 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.
⁸ Swiss Tropical and Public Health Institute, Basel, Switzerland.
⁹ University of Basel, Basel, Switzerland.
¹⁰ National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, USA.
¹¹ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
¹² Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
¹³ Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
¹⁴ Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
¹⁵ Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
¹⁶ TUM School of Medicine, Technical University of Munich, Munich, Germany.
¹⁷ Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, 33520, Tampere, Finland.
¹⁸ Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
¹⁹ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
²⁰ Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
²¹ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, USA.
²² Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²³ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
²⁴ MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
²⁵ Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
²⁶ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
²⁷ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
²⁸ Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
²⁹ Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
³⁰ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
³¹ Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
³² Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria, 3004, Australia.
³³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
³⁴ Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
³⁵ National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
³⁶ Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
³⁷ School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
³⁸ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, 3168, Australia.
³⁹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, 207 Bouverie Street, Melbourne, Victoria, 3010, Australia.
⁴⁰ Department of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05446, USA.
⁴¹ Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, 33521, Tampere, Finland.
⁴² Children's Minnesota Research Institute, Children's Minnesota, Minneapolis, MN, 55404, USA.
⁴³ Department of Biostatistics, Boston University School of Public Health, Boston, USA.
⁴⁴ NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, SE1 9RT, UK.
⁴⁵ Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
⁴⁶ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
⁴⁷ Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
⁴⁸ Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
⁴⁹ German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
⁵⁰ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁵¹ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
⁵² Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁵³ Department of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
⁵⁴ Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
⁵⁵ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁵⁶ Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
⁵⁷ Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55101, Mainz, Germany.
⁵⁸ Chair of Genetic Epidemiology, Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
⁵⁹ MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
⁶⁰ Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
⁶¹ Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
⁶² Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁶³ Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
⁶⁴ Department of Bioinformatics, Institute of Health Sciences, Hacettepe University, 06100, Ankara, Turkey.
⁶⁵ Deans Office, College of Public Health, University of Kentucky, Lexington, UK.
⁶⁶ Geriatric Unit, Azienda Sanitaria Toscana Centro, Florence, Italy.
⁶⁷ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
⁶⁸ Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawai'i Cancer Center, University of Hawai'i, Honolulu, HI, USA.
⁶⁹ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
⁷⁰ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
⁷¹ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Crewe Rd. South, Edinburgh, EH4 2XU, UK.
⁷² Dept of Epidemiology, University of Alabama at Birmingham, Birmingham, USA.
⁷³ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁷⁴ Bristol NIHR Biomedical Research Centre, Bristol, UK.
⁷⁵ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁷⁶ Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.
⁷⁷ Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.
⁷⁸ 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.

^# Contributed equally.

PMID: 34187551
PMCID: PMC8243879
DOI: 10.1186/s13059-021-02398-9

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

Daniel L McCartney et al. Genome Biol. 2021.

. 2021 Jun 29;22(1):194.

doi: 10.1186/s13059-021-02398-9.

Authors

Affiliations

¹ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK.
² MRC Integrative Epidemiology Unit University of Bristol, Bristol, UK.
³ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁴ Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁵ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁶ Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
⁷ 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.
⁸ Swiss Tropical and Public Health Institute, Basel, Switzerland.
⁹ University of Basel, Basel, Switzerland.
¹⁰ National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, USA.
¹¹ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
¹² Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
¹³ Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
¹⁴ Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
¹⁵ Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
¹⁶ TUM School of Medicine, Technical University of Munich, Munich, Germany.
¹⁷ Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, 33520, Tampere, Finland.
¹⁸ Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
¹⁹ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
²⁰ Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
²¹ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, USA.
²² Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²³ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
²⁴ MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
²⁵ Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
²⁶ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
²⁷ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
²⁸ Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
²⁹ Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
³⁰ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
³¹ Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
³² Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria, 3004, Australia.
³³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
³⁴ Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
³⁵ National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
³⁶ Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
³⁷ School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
³⁸ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, 3168, Australia.
³⁹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, 207 Bouverie Street, Melbourne, Victoria, 3010, Australia.
⁴⁰ Department of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05446, USA.
⁴¹ Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, 33521, Tampere, Finland.
⁴² Children's Minnesota Research Institute, Children's Minnesota, Minneapolis, MN, 55404, USA.
⁴³ Department of Biostatistics, Boston University School of Public Health, Boston, USA.
⁴⁴ NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, SE1 9RT, UK.
⁴⁵ Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
⁴⁶ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
⁴⁷ Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
⁴⁸ Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
⁴⁹ German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
⁵⁰ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁵¹ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
⁵² Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁵³ Department of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
⁵⁴ Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
⁵⁵ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁵⁶ Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
⁵⁷ Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55101, Mainz, Germany.
⁵⁸ Chair of Genetic Epidemiology, Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
⁵⁹ MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
⁶⁰ Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
⁶¹ Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
⁶² Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁶³ Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
⁶⁴ Department of Bioinformatics, Institute of Health Sciences, Hacettepe University, 06100, Ankara, Turkey.
⁶⁵ Deans Office, College of Public Health, University of Kentucky, Lexington, UK.
⁶⁶ Geriatric Unit, Azienda Sanitaria Toscana Centro, Florence, Italy.
⁶⁷ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
⁶⁸ Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawai'i Cancer Center, University of Hawai'i, Honolulu, HI, USA.
⁶⁹ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
⁷⁰ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
⁷¹ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Crewe Rd. South, Edinburgh, EH4 2XU, UK.
⁷² Dept of Epidemiology, University of Alabama at Birmingham, Birmingham, USA.
⁷³ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁷⁴ Bristol NIHR Biomedical Research Centre, Bristol, UK.
⁷⁵ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁷⁶ Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.
⁷⁷ Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.
⁷⁸ 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.

^# Contributed equally.

PMID: 34187551
PMCID: PMC8243879
DOI: 10.1186/s13059-021-02398-9

Abstract

Background: Biological 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.

Results: Leveraging 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.

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

Keywords: DNA methylation; Epigenetic clock; GWAS.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
Genetic correlations and standard errors for the epigenetic biomarkers. IEAA (intrinsic epigenetic age acceleration)

**Fig. 2**
Significant genetic correlations between GrimAge acceleration (A) and PhenoAge acceleration (B) and a selection of GWAS traits. *This variable was originally coded with a high score representing lower health rating. We have multiplied the genetic correlation by − 1 for interpretability

**Fig. 3**
A Polygenic predictions for the six epigenetic biomarkers in LBC1921, LBC1936, SABRE, Born in Bradford, ARIES, FHS, and the Young Finns Study. IEAA (intrinsic epigenetic age acceleration), PAI1 (plasminogen activator inhibitor-1). B Associations between GrimAge polygenic risk score (P < 1) and UK Biobank GWAS traits

**Fig. 4**
Causal effects of UK Biobank GWAS traits on GrimAge acceleration. Effects correspond to increase/decrease in GrimAge acceleration per SD increase in waist circumference, hip circumference, and BMI; or per log odds increase for university/college education and current smoker status

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous