The Relationship Between Epigenetic Age and Myocardial Infarction/Acute Coronary Syndrome in a Population-Based Nested Case-Control Study

Overview

Journal J Pers Med

Date 2022 Jan 21

PMID 35055425

Authors

Sofia Malyutina

Olga Chervova

Taavi Tillmann

Vladimir Maximov

Andrew Ryabikov

Valery Gafarov

Jaroslav A Hubacek

Hynek Pikhart

Stephan Beck

Martin Bobak

Affiliations

Soon will be listed here.

Abstract

We investigated the relationship between 'epigenetic age' (EA) derived from DNA methylation (DNAm) and myocardial infarction (MI)/acute coronary syndrome (ACS). A random population sample was examined in 2003/2005 ( = 9360, 45-69, the HAPIEE project) and followed up for 15 years. From this cohort, incident MI/ACS (cases, = 129) and age- and sex-stratified controls ( = 177) were selected for a nested case-control study. Baseline EA (Horvath's, Hannum's, PhenoAge, Skin and Blood) and the differences between EA and chronological age (CA) were calculated (ΔAHr, ΔAHn, ΔAPh, ΔASB). EAs by Horvath's, Hannum's and Skin and Blood were close to CA (median absolute difference, MAD, of 1.08, -1.91 and -2.03 years); PhenoAge had MAD of -9.29 years vs. CA. The adjusted odds ratios (ORs) of MI/ACS per 1-year increments of ΔAHr, ΔAHn, ΔASB and ΔAPh were 1.01 (95% CI 0.95-1.07), 1.01 (95% CI 0.95-1.08), 1.02 (95% CI 0.97-1.06) and 1.01 (0.93-1.09), respectively. When classified into tertiles, only the highest tertile of ΔAPh showed a suggestion of increased risk of MI/ACS with OR 2.09 (1.11-3.94) independent of age and 1.84 (0.99-3.52) in the age- and sex-adjusted model. Metabolic modulation may be the likely mechanism of this association. In conclusion, this case-control study nested in a prospective population-based cohort did not find strong associations between accelerated epigenetic age markers and risk of MI/ACS. Larger cohort studies are needed to re-examine this important research question.

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References

Wang C, Ni W, Yao Y, Just A, Heiss J, Wei Y . DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4. EBioMedicine. 2020; 63:103151. PMC: 7724153. DOI: 10.1016/j.ebiom.2020.103151. View

Levine M, Lu A, Quach A, Chen B, Assimes T, Bandinelli S . An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018; 10(4):573-591. PMC: 5940111. DOI: 10.18632/aging.101414. View

Xia Y, Brewer A, Bell J . DNA methylation signatures of incident coronary heart disease: findings from epigenome-wide association studies. Clin Epigenetics. 2021; 13(1):186. PMC: 8501606. DOI: 10.1186/s13148-021-01175-6. View

Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S . Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2012; 49(2):359-367. PMC: 3780611. DOI: 10.1016/j.molcel.2012.10.016. View

Xu Z, Langie S, De Boever P, Taylor J, Niu L . RELIC: a novel dye-bias correction method for Illumina Methylation BeadChip. BMC Genomics. 2017; 18(1):4. PMC: 5209853. DOI: 10.1186/s12864-016-3426-3. View

Weidner C, Lin Q, Koch C, Eisele L, Beier F, Ziegler P . Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol. 2014; 15(2):R24. PMC: 4053864. DOI: 10.1186/gb-2014-15-2-r24. View

Horvath S, Zhang Y, Langfelder P, Kahn R, Boks M, van Eijk K . Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol. 2012; 13(10):R97. PMC: 4053733. DOI: 10.1186/gb-2012-13-10-r97. View

Stefler D, Brett D, Sarkadi-Nagy E, Kopczynska E, Detchev S, Bati A . Traditional Eastern European diet and mortality: prospective evidence from the HAPIEE study. Eur J Nutr. 2020; 60(2):1091-1100. PMC: 7900332. DOI: 10.1007/s00394-020-02319-9. View

Peasey A, Bobak M, Kubinova R, Malyutina S, Pajak A, Tamosiunas A . Determinants of cardiovascular disease and other non-communicable diseases in Central and Eastern Europe: rationale and design of the HAPIEE study. BMC Public Health. 2006; 6:255. PMC: 1626086. DOI: 10.1186/1471-2458-6-255. View

10.

Lee Y, Haftorn K, Denault W, Nustad H, Page C, Lyle R . Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array. BMC Genomics. 2020; 21(1):747. PMC: 7590728. DOI: 10.1186/s12864-020-07168-8. View

11.

Horvath S . DNA methylation age of human tissues and cell types. Genome Biol. 2013; 14(10):R115. PMC: 4015143. DOI: 10.1186/gb-2013-14-10-r115. View

12.

Tillmann T, Pikhart H, Peasey A, Kubinova R, Pajak A, Tamosiunas A . Psychosocial and socioeconomic determinants of cardiovascular mortality in Eastern Europe: A multicentre prospective cohort study. PLoS Med. 2017; 14(12):e1002459. PMC: 5718419. DOI: 10.1371/journal.pmed.1002459. View

13.

Horvath S, Raj K . DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018; 19(6):371-384. DOI: 10.1038/s41576-018-0004-3. View

14.

Chervova O, Conde L, Guerra-Assuncao J, Moghul I, Webster A, Berner A . The Personal Genome Project-UK, an open access resource of human multi-omics data. Sci Data. 2019; 6(1):257. PMC: 6823446. DOI: 10.1038/s41597-019-0205-4. View

15.

Christiansen L, Lenart A, Tan Q, Vaupel J, Aviv A, McGue M . DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell. 2015; 15(1):149-54. PMC: 4717264. DOI: 10.1111/acel.12421. View

16.

Fransquet P, Wrigglesworth J, Woods R, Ernst M, Ryan J . The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis. Clin Epigenetics. 2019; 11(1):62. PMC: 6458841. DOI: 10.1186/s13148-019-0656-7. View

17.

Horvath S, Erhart W, Brosch M, Ammerpohl O, von Schonfels W, Ahrens M . Obesity accelerates epigenetic aging of human liver. Proc Natl Acad Sci U S A. 2014; 111(43):15538-43. PMC: 4217403. DOI: 10.1073/pnas.1412759111. View

18.

Roetker N, Pankow J, Bressler J, Morrison A, Boerwinkle E . Prospective Study of Epigenetic Age Acceleration and Incidence of Cardiovascular Disease Outcomes in the ARIC Study (Atherosclerosis Risk in Communities). Circ Genom Precis Med. 2018; 11(3):e001937. PMC: 5863591. DOI: 10.1161/CIRCGEN.117.001937. View

19.

Perna L, Zhang Y, Mons U, Holleczek B, Saum K, Brenner H . Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clin Epigenetics. 2016; 8:64. PMC: 4891876. DOI: 10.1186/s13148-016-0228-z. View

20.

Ryan J, Wrigglesworth J, Loong J, Fransquet P, Woods R . A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated With DNA Methylation Age. J Gerontol A Biol Sci Med Sci. 2019; 75(3):481-494. PMC: 7328212. DOI: 10.1093/gerona/glz099. View