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 editorsMcCartney, 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 seriesGenome Biology

ISSN1474-7596

eISSN1474-760X

Publication year2021

Publication date29/06/2021

Volume22

Article number194

PublisherBiomed Central

Publication countryUnited Kingdom

Publication languageEnglish

DOIhttps://doi.org/10.1186/s13059-021-02398-9

Publication open accessOpenly available

Publication channel open accessOpen Access channel

Publication is parallel published (JYX)https://jyx.jyu.fi/handle/123456789/77041


Abstract

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.


KeywordsageingepigeneticsDNA methylationbiomarkersgenomics

Free keywords DNA methylation; GWAS; epigenetic clock


Contributing organizations


Ministry reportingYes

Reporting Year2021

JUFO rating3


Last updated on 2024-03-04 at 19:47