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

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,Rosie M. 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 J.C. de Geus,Sarah E. Harris,Gibran Hemani,Medea Imboden,Mika Kähönen,Sharon L.R. 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,Kaare Christensen,Karen N. Conneely,Paul Elliott,Luigi Ferrucci,Myriam Fornage,Sara Hägg,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

bioRxiv（2020）

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摘要

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.

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