Novel age-associated DNA methylation changes and epigenetic age acceleration in middle-aged African Americans and whites - PubMed (original) (raw)

Comparative Study

Novel age-associated DNA methylation changes and epigenetic age acceleration in middle-aged African Americans and whites

Salman M Tajuddin et al. Clin Epigenetics. 2019.

Abstract

Background: African Americans (AAs) experience premature chronic health outcomes and longevity disparities consistent with an accelerated aging phenotype. DNA methylation (DNAm) levels at specific CpG positions are hallmarks of aging evidenced by the presence of age-associated differentially methylated CpG positions (aDMPs) that are the basis for the epigenetic clock for measuring biological age acceleration. Since DNAm has not been widely studied among non-European populations, we examined the association between DNAm and chronological age in AAs and whites, and the association between race, poverty, sex, and epigenetic age acceleration.

Results: We measured genome-wide DNA methylation (866,836 CpGs) using the Illumina MethylationEPIC BeadChip in blood DNA extracted from 487 middle-aged AA (N = 244) and white (N = 243), men (N = 248), and women (N = 239). The mean (sd) age was 48.4 (8.8) in AA and 49.0 (8.7) in whites (p = 0.48). We identified 4930 significantly associated aDMPs in AAs and 469 in whites. Of these, 75.6% and 53.1% were novel, largely driven by the increased number of measured CpGs in the EPIC array, in AA and whites, respectively. AAs had more age-associated DNAm changes than whites in genes implicated in age-related diseases and cellular pathways involved in growth and development. We assessed three epigenetic age acceleration measures (universal, intrinsic, and extrinsic). AAs had a significantly slower extrinsic aging compared to whites. Furthermore, compared to AA women, both AA and white men had faster aging in the universal age acceleration measure (+ 2.04 and + 1.24 years, respectively, p < 0.05).

Conclusions: AAs have more wide-spread methylation changes than whites. Race and sex interact to underlie biological age acceleration suggesting altered DNA methylation patterns may be important in age-associated health disparities.

Keywords: African Americans; Aging; Biological age; DNA methylation; Epigenetic clock; Epigenetics; Epigenome-wide association study; European ancestry; Health disparities; Race.

PubMed Disclaimer

Conflict of interest statement

MAN’s participation in this study is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, Maryland. MAN also consults for Illumina Inc., the Michael J. Fox Foundation, and University of California Healthcare. All other authors declare that they have no competing interests.

Figures

Fig. 1

Fig. 1

Distribution of age-associated differentially methylated CpG positions (aDMPs) with their effect size in beta values and significance p value in the African American (AA) and white participants of the HANDLS study: a Manhattan plot in AAs, b Manhattan plot in whites, c volcano plot in AAs, and d volcano plot in whites

Fig. 2

Fig. 2

Venn diagrams of significantly age-associated differentially methylated CpG positions (aDMPs) in African Americans (AAs) and whites: a overlap of aDMPs between AAs and whites, b overlap of aDMPs that were hypermethylated with age, and c overlap of aDMPs that were hypomethylated with age

Fig. 3

Fig. 3

Correlation between DNA methylation-predicted age based on the Horvath and the Hannum clocks, and chronological age in the HANDLS study. Abbreviation: AAs: African Americans

Fig. 4

Fig. 4

Associations between epigenetic age acceleration measures and sex, race, and poverty status. a Sex, b race, and c poverty status. Abbreviations: AAs: African Americans; AgeAccel: universal age acceleration measures; IEAA: intrinsic epigenetic age acceleration; and EEAA: extrinsic epigenetic age acceleration

Fig. 5

Fig. 5

Interaction plots of the association between sex, race, and three measures of epigenetic age acceleration. a AgeAccel, b IEAA, and c EEAA. Abbreviations: AAs: African Americans; AgeAccel: universal age acceleration measures; IEAA: intrinsic epigenetic age acceleration; and EEAA: extrinsic epigenetic age acceleration

Similar articles

Cited by

References

    1. Murray CJ, Kulkarni SC, Michaud C, Tomijima N, Bulzacchelli MT, Iandiorio TJ, Ezzati M. Eight Americas: investigating mortality disparities across races, counties, and race-counties in the United States. PLoS Med. 2006;3:e260. doi: 10.1371/journal.pmed.0030260. - DOI - PMC - PubMed
    1. Bilal U, Diez-Roux AV. Troubling trends in health disparities. N Engl J Med. 2018;378:1557–1558. doi: 10.1056/NEJMc1800328. - DOI - PubMed
    1. Levine ME, Crimmins EM. Evidence of accelerated aging among African Americans and its implications for mortality. Soc Sci Med. 2014;118:27–32. doi: 10.1016/j.socscimed.2014.07.022. - DOI - PMC - PubMed
    1. Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2012;13:97–109. doi: 10.1038/nrg3142. - DOI - PubMed
    1. Tajuddin SM, Amaral AF, Fernandez AF, Rodriguez-Rodero S, Rodriguez RM, Moore LE, Tardon A, Carrato A, Garcia-Closas M, Silverman DT, et al. Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA. Environ Health Perspect. 2013;121:650–656. doi: 10.1289/ehp.1206068. - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources