Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing
Author:
McCartney Daniel L.ORCID, Min Josine L., Richmond Rebecca C., Lu Ake T., Sobczyk Maria K., Davies Gail, Broer Linda, Guo Xiuqing, Jeong Ayoung, Jung Jeesun, Kasela Silva, Katrinli Seyma, Kuo Pei-Lun, Matias-Garcia Pamela R., Mishra Pashupati P., Nygaard Marianne, Palviainen Teemu, Patki Amit, Raffield Laura M., Ratliff Scott M., Richardson Tom G., Robinson Oliver, Soerensen Mette, Sun Dianjianyi, Tsai Pei-Chien, van der Zee Matthijs D., Walker Rosie M.ORCID, Wang Xiaochuan, Wang Yunzhang, Xia Rui, Xu Zongli, Yao Jie, Zhao Wei, Correa Adolfo, Boerwinkle Eric, Dugué Pierre-Antoine, Durda Peter, Elliott Hannah R, Gieger Christian, de Geus Eco J.C., Harris Sarah E., Hemani Gibran, Imboden Medea, Kähönen Mika, Kardia Sharon L.R., Kresovich Jacob K., Li Shengxu, Lunetta Kathryn L., Mangino Massimo, Mason Dan, McIntosh Andrew M.ORCID, Mengel-From Jonas, Moore Ann Zenobia, Murabito Joanne M., Ollikainen Miina, Pankow James S., Pedersen Nancy L., Peters Annette, Polidoro Silvia, Porteous David J., Raitakari Olli, Rich Stephen S., Sandler Dale P., Sillanpää Elina, Smith Alicia K, Southey Melissa C., Strauch Konstantin, Tiwari Hemant, Tanaka Toshiko, Tillin Therese, Uitterlinden Andre G, Van Den Berg David J., van Dongen Jenny, Wilson James G., Wright John, Yet Idil, Arnett Donna, Bandinelli Stefania, Bell Jordana T., Binder Alexandra M, Boomsma Dorret IORCID, Chen Wei, Christensen KaareORCID, Conneely Karen N., Elliott PaulORCID, Ferrucci Luigi, Fornage MyriamORCID, Hägg Sara, Hayward Caroline, Irvin Marguerite, Kaprio Jaakko, Lawlor Deborah A., Lehtimäki Terho, Lohoff Falk W., Milani Lili, Milne Roger L., Probst-Hensch Nicole, Reiner Alex P., Ritz BeateORCID, Rotter Jerome I., Smith Jennifer A., Taylor Jack A., van Meurs Joyce B.J., Vineis Paolo, Waldenberger Melanie, Deary Ian J., Relton Caroline L., Horvath Steve, Marioni Riccardo E., ,
Abstract
AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic architecture underlying epigenetic ageing and its shared genetic contributions with lifestyle factors and longevity.
Publisher
Cold Spring Harbor Laboratory
Cited by
10 articles.
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