Systematic underestimation of the epigenetic clock and age acceleration in older subjects
Abstract Background The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments. Results The model systematically underestimates age...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-12-01
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| Series: | Genome Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13059-019-1810-4 |
| _version_ | 1818920945090297856 |
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| author | Louis Y. El Khoury Tyler Gorrie-Stone Melissa Smart Amanda Hughes Yanchun Bao Alexandria Andrayas Joe Burrage Eilis Hannon Meena Kumari Jonathan Mill Leonard C. Schalkwyk |
| author_facet | Louis Y. El Khoury Tyler Gorrie-Stone Melissa Smart Amanda Hughes Yanchun Bao Alexandria Andrayas Joe Burrage Eilis Hannon Meena Kumari Jonathan Mill Leonard C. Schalkwyk |
| author_sort | Louis Y. El Khoury |
| collection | DOAJ |
| description | Abstract Background The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments. Results The model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, and this can lead to spurious associations. The current literature includes examples of association tests with age acceleration calculated in a wide variety of ways. Conclusions The concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate. |
| first_indexed | 2024-12-20T01:29:48Z |
| format | Article |
| id | doaj.art-e6858c0976d94ec39b1624f1fc0daea6 |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-12-20T01:29:48Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-e6858c0976d94ec39b1624f1fc0daea62022-12-21T19:58:08ZengBMCGenome Biology1474-760X2019-12-0120111010.1186/s13059-019-1810-4Systematic underestimation of the epigenetic clock and age acceleration in older subjectsLouis Y. El Khoury0Tyler Gorrie-Stone1Melissa Smart2Amanda Hughes3Yanchun Bao4Alexandria Andrayas5Joe Burrage6Eilis Hannon7Meena Kumari8Jonathan Mill9Leonard C. Schalkwyk10School of Life Sciences, University of EssexSchool of Life Sciences, University of EssexInstitute for Social and Economic Research, University of EssexMRC Integrative Epidemiology Unit - University of BristolInstitute for Social and Economic Research, University of EssexSchool of Life Sciences, University of EssexMedical School, University of ExeterMedical School, University of ExeterInstitute for Social and Economic Research, University of EssexMedical School, University of ExeterSchool of Life Sciences, University of EssexAbstract Background The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments. Results The model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, and this can lead to spurious associations. The current literature includes examples of association tests with age acceleration calculated in a wide variety of ways. Conclusions The concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate.https://doi.org/10.1186/s13059-019-1810-4DNA methylationEpigenetic clockAge acceleration |
| spellingShingle | Louis Y. El Khoury Tyler Gorrie-Stone Melissa Smart Amanda Hughes Yanchun Bao Alexandria Andrayas Joe Burrage Eilis Hannon Meena Kumari Jonathan Mill Leonard C. Schalkwyk Systematic underestimation of the epigenetic clock and age acceleration in older subjects Genome Biology DNA methylation Epigenetic clock Age acceleration |
| title | Systematic underestimation of the epigenetic clock and age acceleration in older subjects |
| title_full | Systematic underestimation of the epigenetic clock and age acceleration in older subjects |
| title_fullStr | Systematic underestimation of the epigenetic clock and age acceleration in older subjects |
| title_full_unstemmed | Systematic underestimation of the epigenetic clock and age acceleration in older subjects |
| title_short | Systematic underestimation of the epigenetic clock and age acceleration in older subjects |
| title_sort | systematic underestimation of the epigenetic clock and age acceleration in older subjects |
| topic | DNA methylation Epigenetic clock Age acceleration |
| url | https://doi.org/10.1186/s13059-019-1810-4 |
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