Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing
McCartney, D. L.; Min, J. L.; Richmond, R. C.; Lu, A. T.; Sobczyk, M. K.; Davies, G.; Broer, L.; Guo, X.; Jeong, A.; Jung, J.; Kasela, S.; Katrinli, S.; Kuo, P.-L.; Matias-Garcia, P. R.; Mishra, P. P.; Nygaard, M.; Palviainen, T.; Patki, A.; Raffield, L. M.; Ratliff, S. M.; Richardson, T.; Robinson, O.; Soerensen, M.; Sun, D.; Tsai, P.-C.; van der Zee, M. D.; Walker, R. M.; Wang, X.; Wang, Y.; Xia, R.; Xu, Z.; Yao, J.; Zhao, W.; Correa, A.; Boerwinkle, E.; Dugue, P.-A.; Durda, P.; Elliott, H. R.; Gieger, C.; The Genetics of DNA Methylation Consortium (GoDMC), ; de Geus, E. J.; Harris, S. E.;
Show 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.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.