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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, 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 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, 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

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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