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

Description

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.
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Year of publication

2021

Type of data

Authors

Mika Kähönen - Creator

Pashupati Mishra - Creator

Terho Lehtimäki - Creator

Unknown organization

Adolfo Correa - Creator

Ake T. Lu - Creator

Alex P. Reiner - Creator

Alexandra M. Binder - Creator

Alicia K. Smith - Creator

Amit Patki - Creator

Andre G. Uitterlinden - Creator

Andrew M. McIntosh - Creator

Ann Zenobia Moore - Creator

Annette Peters - Creator

Ayoung Jeong - Creator

Beate Ritz - Creator

Caroline Hayward - Creator

Caroline L. Relton - Creator

Christian Gieger - Creator

Dale P. Sandler - Creator

Dan Mason - Creator

Daniel L. McCartney - Creator

David J. Porteous - Creator

David J. Van Den Berg - Creator

Deborah A. Lawlor - Creator

Dianjianyi Sun - Creator

Donna Arnett - Creator

Dorret I. Boomsma - Creator

Eco J. C. de Geus - Creator

Elina Sillanpää - Creator

Eric Boerwinkle - Creator

Falk W. Lohoff - Creator

Gail Davies - Creator

Gibran Hemani - Creator

Hannah R. Elliott - Creator

Hemant Tiwari - Creator

Ian J. Deary - Creator

Idil Yet - Creator

Jaakko Kaprio - Creator

Jack A. Taylor - Creator

Jacob K. Kresovich - Creator

James G. Wilson - Creator

James S. Pankow - Creator

Jeesun Jung - Creator

Jennifer A. Smith - Creator

Jenny van Dongen - Creator

Jerome I. Rotter - Creator

Jie Yao - Creator

Joanne M. Murabito - Creator

John Wright - Creator

Jonas Mengel-From - Creator

Jordana T. Bell - Creator

Josine L. Min - Creator

Joyce B. J. van Meurs - Creator

Kaare Christensen - Creator

Karen N. Conneely - Creator

Kathryn L. Lunetta - Creator

Konstantin Strauch - Creator

Laura M. Raffield - Creator

Lili Milani - Creator

Linda Broer - Creator

Luigi Ferrucci - Creator

Marguerite Irvin - Creator

Maria K. Sobczyk - Creator

Marianne Nygaard - Creator

Massimo Mangino - Creator

Matthijs D. van der Zee - Creator

Medea Imboden - Creator

Melanie Waldenberger - Creator

Melissa C. Southey - Creator

Mette Soerensen - Creator

Miina Ollikainen - Creator

Myriam Fornage - Creator

Nancy L. Pedersen - Creator

Nicole Probst-Hensch - Creator

Oliver Robinson - Creator

Olli Raitakari - Creator

Pamela R. Matias-Garcia - Creator

Paolo Vineis - Creator

Paul Elliott - Creator

Pei-Chien Tsai - Creator

Pei-Lun Kuo - Creator

Peter Durda - Creator

Pierre-Antoine Dugué - Creator

Rebecca C. Richmond - Creator

Riccardo E. Marioni - Creator

Roger L. Milne - Creator

Rosie M. Walker - Creator

Rui Xia - Creator

Sara Hägg - Creator

Sarah E. Harris - Creator

Scott M. Ratliff - Creator

Seyma Katrinli - Creator

Sharon L. R. Kardia - Creator

Shengxu Li - Creator

Silva Kasela - Creator

Silvia Polidoro - Creator

Stefania Bandinelli - Creator

Stephen S. Rich - Creator

Steve Horvath - Creator

Teemu Palviainen - Creator

Therese Tillin - Creator

Tom G. Richardson - Creator

Toshiko Tanaka - Creator

Wei Chen - Creator

Wei Zhao - Creator

Xiaochuan Wang - Creator

Xiuqing Guo - Creator

Yunzhang Wang - Creator

Zongli Xu - Creator

figshare - Publisher

Project

Other information

Fields of science

Biomedicine

Language

English

Open access

Open

License

Creative Commons Attribution 4.0 International (CC BY 4.0)

Keywords

Biomedicine

Subject headings

Temporal coverage

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