Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing
By
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,
Silva Kasela,
Seyma Katrinli,
Pei-Lun Kuo,
Pamela R Matias-Garcia,
Pashupati P. Mishra,
Marianne Nygaard,
Teemu Palviainen,
Amit Patki,
Laura M Raffield,
Scott M Ratliff,
Tom G Richardson,
Oliver Robinson,
Mette Soerensen,
Dianjianyi Sun,
Pei-Chien Tsai,
Matthijs D. van der Zee,
RM Walker,
Xiaochuan Wang,
Yunzhang Wang,
Rui Xia,
Zongli Xu,
Jie Yao,
Wei Zhao,
Adolfo Correa,
Eric Boerwinkle,
Pierre-Antoine Dugué,
Peter Durda,
Hannah R Elliott,
Christian Gieger,
The Genetics of DNA Methylation Consortium,
Eco JC de Geus,
Sarah E. Harris,
Gibran Hemani,
Medea Imboden,
Mika Kähönen,
Sharon LR Kardia,
Jacob K Kresovich,
Shengxu Li,
Kathryn L. Lunetta,
Massimo Mangino,
Dan Mason,
Andrew M. McIntosh,
Jonas Mengel-From,
Ann Zenobia Moore,
Joanne M Murabito,
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,
Miina Ollikainen,
James S Pankow,
Nancy L. Pedersen,
Annette Peters,
Silvia Polidoro,
David J. Porteous,
Olli Raitakari,
Stephen S Rich,
Dale P Sandler,
Elina Sillanpää,
Alicia K Smith,
Melissa C Southey,
Konstantin Strauch,
Hemant Tiwari,
Toshiko Tanaka,
Therese Tillin,
Andre G Uitterlinden,
David J. Van Den Berg,
Jenny van Dongen,
James G Wilson,
John Wright,
Idil Yet,
Donna Arnett,
Stefania Bandinelli,
Jordana T. Bell,
Alexandra M Binder,
Dorret I. Boomsma,
Wei Chen,
John R. Shaffer,
Karen N Conneely,
Paul Elliott,
Luigi Ferrucci,
Myriam Fornage,
Sara Hagg,
Caroline Hayward,
Marguerite Irvin,
Jaakko Kaprio,
Deborah A. Lawlor,
Terho Lehtimäki,
Falk W Lohoff,
Lili Milani,
Roger L. Milne,
Nicole Probst-Hensch,
Alex P Reiner,
Beate Ritz,
Jerome I. Rotter,
Jennifer A. Smith,
Jack A Taylor,
Joyce B.J. van Meurs,
Paolo Vineis,
Melanie Waldenberger,
Ian J Deary,
Caroline L Relton,
Steve Horvath,
Riccardo E Marioni
Posted 30 Jun 2020
bioRxiv DOI: 10.1101/2020.06.29.133702
Biological ageing estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. We report 137 genome wide significant loci (113 novel) via meta-analyses of six DNA methylation-based (DNAm) biomarkers in 34,962 European-ancestries and 6,482 African American individuals. Several DNAm biomarkers exhibit strong genetic correlations with multiple health and lifestyle measures. Polygenic scores explained up to 4.2% of the variance and the score for a DNAm estimator of mortality risk, DNAmGrimAge, was associated with parental longevity, education, and adiposity-related traits. Overall, this study greatly advances our understanding of the genetic determinants of epigenetic ageing processes in human blood. ### Competing Interest Statement The authors have declared no competing interest.
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