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

McCartney, D. L. and Min, J. L. and Richmond, R. C. and Lu, A. T. and Sobczyk, M. K. and Davies, G. and Broer, L. and Guo, X. and Jeong, A. and Jung, J. and Kasela, S. and Katrinli, S. and Kuo, P. L. and Matias-Garcia, P. R. and Mishra, P. P. and Nygaard, M. and Palviainen, T. and Patki, A. and Raffield, L. M. and Ratliff, S. M. and Richardson, T. G. and Robinson, O. and Soerensen, M. and Sun, D. and Tsai, P. C. and van der Zee, M. D. and Walker, R. M. and Wang, X. and Wang, Y. and Xia, R. and Xu, Z. and Yao, J. and Zhao, W. and Correa, A. and Boerwinkle, E. and Dugue, P. A. and Durda, P. and Elliott, H. R. and Gieger, C. and Genetics of DNA Methylation Consortium, and de Geus, E. J. C. and Harris, S. E. and Hemani, G. and Imboden, M. and Kahonen, M. and Kardia, S. L. R. and Kresovich, J. K. and Li, S. and Lunetta, K. L. and Mangino, M. and Mason, D. and McIntosh, A. M. and Mengel-From, J. and Moore, A. Z. and Murabito, J. M. and Nhlbi Trans-Omics for Precision Medicine Consortium, and Ollikainen, M. and Pankow, J. S. and Pedersen, N. L. and Peters, A. and Polidoro, S. and Porteous, D. J. and Raitakari, O. and Rich, S. S. and Sandler, D. P. and Sillanpaa, E. and Smith, A. K. and Southey, M. C. and Strauch, K. and Tiwari, H. and Tanaka, T. and Tillin, T. and Uitterlinden, A. G. and Van Den Berg, D. J. and van Dongen, J. and Wilson, J. G. and Wright, J. and Yet, I. and Arnett, D. and Bandinelli, S. and Bell, J. T. and Binder, A. M. and Boomsma, D. I. and Chen, W. and Christensen, K. and Conneely, K. N. and Elliott, P. and Ferrucci, L. and Fornage, M. and Hagg, S. and Hayward, C. and Irvin, M. and Kaprio, J. and Lawlor, D. A. and Lehtimaki, T. and Lohoff, F. W. and Milani, L. and Milne, R. L. and Probst-Hensch, N. and Reiner, A. P. and Ritz, B. and Rotter, J. I. and Smith, J. A. and Taylor, J. A. and van Meurs, J. B. J. and Vineis, P. and Waldenberger, M. and Deary, I. J. and Relton, C. L. and Horvath, S. and Marioni, R. E.. (2021) Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging. Genome Biol, 22. p. 194.

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BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Jeong, Ayoung and Imboden, Medea and Probst-Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1474-760X (Electronic)1474-7596 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Dec 2022 14:19
Deposited On:20 Dec 2022 14:19

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