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.

doi:10.1101/2020.06.29.133702

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bioRxiv · 10.1101/2020.06.29.133702

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

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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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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.. 2020-06-30. Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing. https://doi.org/10.1101/2020.06.29.133702

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