A1 Journal article (refereed)
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging (2021)
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., . . . Marioni, R. E. (2021). Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging. Genome Biology, 22, Article 194. https://doi.org/10.1186/s13059-021-02398-9
JYU authors or editors
Publication details
All authors or editors: McCartney, Daniel L.; Min, Josine L.; Richmond, Rebecca C.; Lu, Ake T.; Sobczyk, Maria K.; Davies, Gail; Broer, Linda; Guo, Xiuqing; Jeong, Ayoung; Jung, Jeesun; et al.
Journal or series: Genome Biology
ISSN: 1474-7596
eISSN: 1474-760X
Publication year: 2021
Publication date: 29/06/2021
Volume: 22
Article number: 194
Publisher: Biomed Central
Publication country: United Kingdom
Publication language: English
DOI: https://doi.org/10.1186/s13059-021-02398-9
Publication open access: Openly available
Publication channel open access: Open Access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/77041
Abstract
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.
Keywords: ageing; epigenetics; DNA methylation; biomarkers; genomics
Free keywords: DNA methylation; GWAS; epigenetic clock
Contributing organizations
Ministry reporting: Yes
Reporting Year: 2021
JUFO rating: 3
