Publication

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

Downloadable Content

Persistent URL
Last modified
  • 05/22/2025
Type of Material
Authors
    Daniel L McCartney, University of EdinburghJosine L Min, University of BristolRebecca Richmond, University of BristolAke T Lu, University of California Los AngelesMaria K Sobczyk, University of BristolGail Davies, University of EdinburghLinda Broer, Erasmus MCXiuqing Guo, Harbor-UCLA Medical Center, TorranceAyoung Jeong, Swiss Tropical and Public Health InstituteJeesun Jung, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, BethesdaSilva Kasela, University of TartuSeyma Katrinli, Emory UniversityPei-Lun Kuo, National Institute on Aging, BaltimorePamela R Matias-Garcia, German Research Center for Environmental HealthPashupati P Mishra, Tampere UniversityMarianne Nygaard, University of Southern DenmarkTeemu Palviainen, University of HelsinkiAmit Patki, University of Alabama BirminghamLaura M Raffield, University of North CarolinaScott M Ratliff, University of MichiganTom G Richardson, University of MichiganOliver Robinson, Imperial College LondonMette Soerensen, University of Southern DenmarkDianjianyi Sun, Peking UniversityPei-Chien Tsai, Kings College LondonMattijs D van der Zee, Vrije Universiteit AmsterdamRosie M Walker, University of EdinburghXiaochuan Wang, Cancer Council VictoriaYunzhang Wang, Karolinska InstitutetRui Xia, University of Texas Health Science Center at HoustonZongli Xu, National Institute of Environmental Health SciencesJie Yao, Harbor-UCLA Medical Center, TorranceWei Zhao, University of MichiganAdolfo Correa, Emory UniversityEric Boerwinkle, University of Texas Health Science Center at HoustonPierre-Antoine Dugué, Cancer Council VictoriaPeter Durda, University of VermontHannah R Elliott, University of BristolChristian Gieger, German Research Center for Environmental HealthEco JC de Geus, Vrije Universiteit AmsterdamSarah E Harris, University of EdinburghGibran Hemani, University of BristolMedea Imboden, Swiss Tropical and Public Health InstituteMika Kähönen, Tampere UniversitySharon LR Kardia, University of MichiganJacob K Kresovich, University of MichiganShengxu Li, Childrens MinnesotaKathryn L Lunetta, Boston UniversityMassimo Mangino, Kings College LondonDan Mason, Bradford Teaching Hospitals NHS Foundation TrustAndrew M McIntosh, University of EdinburghJonas Mengel-From, University of Southern DenmarkAnn Zenobia Moore, National Institute on Aging, BaltimoreJoanne M Murabito, Boston UniversityMiina Ollikainen, University of HelsinkiJames S Pankow, University of Minnesota, MinneapolisNancy L Pedersen, Karolinska InstitutetAnnette Peters, German Research Center for Environmental HealthSilvia Polidoro, Imperial College LondonDavid J Porteous, University of EdinburghOlli Raitakari, University of TurkuStephen S Rich, University of VirginiaDale P Sandler, National Institute of Environmental Health Sciences, Research Triangle ParkElina Sillanpää, University of HelsinkiAlicia Smith, Emory UniversityMelissa C Southey, Cancer Council VictoriaKonstantin Strauch, German Research Center for Environmental HealthHemant Tiwari, University of Alabama BirminghamToshiko Tanaka, National Institute on Aging, BaltimoreTherese Tillin, University College LondonAndre G Uitterlinden, Erasmus MC, Rotterdam, the NetherlandsDavid J van den Berg, University of Southern CaliforniaJenny van Dongen, Vrije Universiteit AmsterdamJames G Wilson, Beth Israel Deaconess Medical Center, BostonJohn Wright, Bradford Teaching Hospitals NHS Foundation TrustIdil Yet, Kings College LondonDonna Arnett, University of KentuckyStefania Bandinelli, Azienda Sanitaria Toscana Centro, FlorenceJordana T Bell, Kings College LondonAlexandra M Binder, University of California Los AngelesDorret I Boomsma, Vrije Universiteit AmsterdamWei Chen, Tulane UniversityKaare Christensen, University of Southern DenmarkKaren Conneely, Emory UniversityPaul Elliott, Imperial College LondonLuigi Ferrucci, National Institute on Aging, BaltimoreMyriam Fornage, University of Texas Health Science Center at HoustonSara Hägg, Karolinska InstitutetCaroline Hayward, University of EdinburghMarguerite Irvin, University of Alabama BirminghamJaakko Kaprio, University of HelsinkiDeborah A Lawlor, University of BristolTerho Lehtimäki, Tampere UniversityFalk W Lohoff, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, BethesdaLili Milani, University of TartuRoger L Milne, Cancer Council VictoriaNicole Probst-Hensch, Swiss Tropical and Public Health InstituteAlex P Reiner, University of WashingtonBeate Ritz, University of California Los AngelesJerome I Rotter, Harbor-UCLA Medical Center, TorranceJennifer Smith, University of MichiganJack A Taylor, National Institute of Environmental Health Sciences, Research Triangle ParkJoyce BJ van Meurs, Erasmus MC, Rotterdam, the NetherlandsPaolo Vineis, Imperial College LondonMelanie Waldenberger, German Research Center for Environmental HealthIan J Deary, University of EdinburghCaroline L Relton, University of BristolSteve Horvath, University of California Los AngelesRiccardo E Marioni, University of Edinburgh
Language
  • English
Date
  • 2021-06-29
Publisher
  • BMC
Publication Version
Copyright Statement
  • © The Author(s) 2021
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 22
Issue
  • 1
Start Page
  • 194
End Page
  • 194
Grant/Funding Information
  • Core support including phenotype harmonization, data management, sample-identity QC, and general program coordination were provided by the TOPMed Data Coordinating Center (R01HL-120393; U01HL-120393; contract HHSN268201800001I).
  • Molecular data for the Trans-Omics in Precision Medicine (TOPMed) program was supported by the National Heart, Lung and Blood Institute (NHLBI).
  • REM and DLM are supported by Alzheimer’s Research UK major project grant, ARUK-PG2017B-10.
  • Core support including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering were provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I).
  • REM, SH, and AL are supported by a National Institute of Health U01 grant, U01AG060908–01.
  • RCR is a de Pass Vice Chancellor’s Research Fellow at the University of Bristol. CR and RCR receive support from a Cancer Research UK Program Grant (C18281/A191169).
  • CLR, JLM, and RCR are members of the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/5).
  • IJD is supported by Age UK (Disconnected Mind program), UKRI Medical Research Council grant, MR/R0245065/1, and by National Institute of Health R01 grant, 1R01AG054628-01A1. GD is supported by the University of Edinburgh School of Philosophy, Psychology and Language Sciences
Supplemental Material (URL)
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.
Author Notes
Keywords
Research Categories
  • Health Sciences, Epidemiology
  • Biology, Biostatistics
  • Health Sciences, Obstetrics and Gynecology

Tools

Relations

In Collection:

Items

Thumbnail Title File Description Date Uploaded Visibility Actions
file details Publication File - vzwgd.pdf Primary Content 2025-05-21 Public Download