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

Daniel L. McCartney; Josine L. Min; Rebecca Claire Richmond; Ake Tzu-Hui Lu; Maria Sobczyk; Gail Davies; Linda Broer; Xiuqing Guo; Ayoung Jeong; Jeesun Jung; Silva Kasela; Şeyma Katrinli; Pei‐Lun Kuo; Pamela R. Matías‐García; Pashupati Prasad 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 May Walker; Xiaochuan Wang; Yunzhang Wang; Rui Xia

doi:10.1101/2020.06.29.133702

GeneticsbioRxivJun 29, 2020

Preprint

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

Daniel L. McCartney iD, Josine L. Min iD, Rebecca Claire Richmond iD, Ake Tzu-Hui Lu iD, Maria Sobczyk iD, Gail Davies iD, Linda Broer iD, Xiuqing Guo iD, Ayoung Jeong iD, Jeesun Jung iD, Silva Kasela iD, Şeyma Katrinli iD, Pei‐Lun Kuo, Pamela R. Matías‐García iD, Pashupati Prasad Mishra iD, Marianne Nygaard iD, Teemu Palviainen iD, Amit Patki iD, Laura M. Raffield iD, Scott M. Ratliff iD, Tom G. Richardson iD, Oliver Robinson iD, Mette Soerensen iD, Dianjianyi Sun iD, Pei-Chien Tsai iD, , Jerome I. Rotter iD

Abstract

Biological 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.

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