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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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