Evaluation of Epigenetic Age Acceleration Scores and Their Associations with CVD-Related Phenotypes in a Population Cohort
Olga Chervova,
Elizabeth Chernysheva ,
Kseniia Panteleeva ,
Tyas Arum Widayati ,
Natalie Hrbkova,
Jadesada Schneider ,
Vladimir Maximov ,
Andrew Ryabikov ,
Taavi Tillmann ,
Hynek Pikhart,
Martin Bobak ,
Vitaly Voloshin ,
Sofia Malyutina ,
Stephan Beck
Affiliations
Olga Chervova
UCL Cancer Institute, University College London, London WC1E 6DD, UK
Elizabeth Chernysheva
Department of Pathology and Biomedical Science, University of Otago, P.O. Box 4345, Christchurch 8140, New Zealand
Kseniia Panteleeva
UCL Cancer Institute, University College London, London WC1E 6DD, UK
Tyas Arum Widayati
UCL Cancer Institute, University College London, London WC1E 6DD, UK
Natalie Hrbkova
UCL Cancer Institute, University College London, London WC1E 6DD, UK
Jadesada Schneider
UCL Cancer Institute, University College London, London WC1E 6DD, UK
Vladimir Maximov
Institute of Internal and Preventive Medicine—Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630089, Russia
Andrew Ryabikov
Institute of Internal and Preventive Medicine—Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630089, Russia
Taavi Tillmann
Institute of Family Medicine and Public Health, 50411 Tartu, Estonia
Hynek Pikhart
Institute of Epidemiology and Health Care, University College London, London WC1E 7HB, UK
Martin Bobak
Institute of Epidemiology and Health Care, University College London, London WC1E 7HB, UK
Vitaly Voloshin
Royal Botanical Gardens Kew, London TW9 3AE, UK
Sofia Malyutina
Institute of Internal and Preventive Medicine—Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630089, Russia
Stephan Beck
UCL Cancer Institute, University College London, London WC1E 6DD, UK
We evaluated associations between nine epigenetic age acceleration (EAA) scores and 18 cardiometabolic phenotypes using an Eastern European ageing population cohort richly annotated for a diverse set of phenotypes (subsample, n = 306; aged 45–69 years). This was implemented by splitting the data into groups with positive and negative EAAs. We observed strong association between all EAA scores and sex, suggesting that any analysis of EAAs should be adjusted by sex. We found that some sex-adjusted EAA scores were significantly associated with several phenotypes such as blood levels of gamma-glutamyl transferase and low-density lipoprotein, smoking status, annual alcohol consumption, multiple carotid plaques, and incident coronary heart disease status (not necessarily the same phenotypes for different EAAs). We demonstrated that even after adjusting EAAs for sex, EAA–phenotype associations remain sex-specific, which should be taken into account in any downstream analysis involving EAAs. The obtained results suggest that in some EAA–phenotype associations, negative EAA scores (i.e., epigenetic age below chronological age) indicated more harmful phenotype values, which is counterintuitive. Among all considered epigenetic clocks, GrimAge was significantly associated with more phenotypes than any other EA scores in this Russian sample.
