Pulse lineResearch With Heart Logo

Cerebral white matter hyperintensities on MRI and acceleration of epigenetic aging: the atherosclerosis risk in communities study.

TitleCerebral white matter hyperintensities on MRI and acceleration of epigenetic aging: the atherosclerosis risk in communities study.
Publication TypeJournal Article
Year of Publication2017
AuthorsRaina A, Zhao X, Grove ML, Bressler J, Gottesman RF, Guan W, Pankow JS, Boerwinkle E, Mosley TH
Secondary AuthorsFornage M
JournalClin Epigenetics
Volume9
Pagination21
Date Published2017
ISSN1868-7083
KeywordsAfrican Americans, Aged, Aging, Algorithms, Atherosclerosis, Body Mass Index, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Female, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Middle Aged, White Matter
Abstract

BACKGROUND: Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are part of the spectrum of brain vascular injury accompanying aging and are associated with a substantial risk of stroke and dementia. We investigated the association of cerebral WMH burden on MRI with a DNA methylation-based biomarker of aging, termed DNA methylation age acceleration, which represents the deviation of the DNA methylation-predicted age from the chronologic age.

RESULTS: In this cross-sectional observational study of 713 African-American participants of the Atherosclerosis Risk in Communities study, aged 51-73 years, estimates of predicted age were obtained based on two algorithms (Hannum et al. and Horvath) from DNA methylation measured using the Illumina HM450 array on genomic DNA extracted from blood. Age acceleration, calculated as the residual values from the regression of each of the predicted age measures onto the chronologic age, was significantly associated with WMH burden after accounting for chronologic age and sex, body mass index, systolic blood pressure, hypertension, diabetes, current smoking, and blood cell composition, and results were similar for either Hannum et al.- or Horvath-derived estimates ( = 0.016 and 0.026). An age acceleration increase by 1 year was associated with an increase of WMH burden by ~1 grade. To shed light on possible biological mechanisms underlying this association, we conducted a genome-wide association study of age acceleration and identified four loci harboring genes implicated in hemostasis, cell proliferation, protein degradation, and histone methylation. However, none of these loci were associated with WMH burden.

CONCLUSIONS: In this population-based study of middle-aged to older African-American adults, we report an association between accelerated epigenetic aging and increased WMH burden, independent of known risk factors, including chronologic age. Additional studies are needed to clarify whether DNA methylation age reflects biological mechanisms implicated in the aging of the cerebral white matter.

DOI10.1186/s13148-016-0302-6
Alternate JournalClin Epigenetics
PubMed ID28289478
PubMed Central IDPMC5310061
Grant ListHHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States