Study identifies DNA signatures linked to heart disease

Date:
August 4, 2021
Source:
Columbia University's Mailman School of Public Health
Summary:
A new study identifies DNA signatures associated with risk for
cardiovascular disease, a discovery that could lead to opportunities
for clinical intervention years before symptoms manifest.



FULL STORY ==========================================================================
A new study identifies DNA signatures associated with risk for
cardiovascular disease, a discovery that could lead to opportunities for clinical intervention years before symptoms manifest. Based on analyses
of data from five large heart cohort studies of diverse populations,
the findings are published in the journal JAMA Cardiology.


==========================================================================
"The science is rapidly advancing in the area of epigenetics --
modifications to our DNA that are often environmentally driven and
have the potential to serve as early warning sign for disease," says
Ana Navas-Acien, MD, PhD, the study's first author and professor of environmental health sciences at Columbia University Mailman School of
Public Health. "In this study, we harness the country's best clinical
data on heart disease from diverse populations to begin to unlock the
specific epigenetic changes involved the complex biology that leads to
disease. Ultimately, we hope the research will allow us to identify
and prevent disease before the worst damage takes place, although
developing appropriate DNA methylation tests is still years away."
The researchers began their analysis with data from the Strong Heart
Study, the largest study of cardiovascular disease in American Indians, conducted in partnership with communities across the Great Plains and the Southwest since 1988. They analyzed blood samples to identify specific locations on DNA where methylation activity was associated with incidents
of coronary heart disease, including heart attack and coronary deaths (methylation can change the activity of a DNA segment without changing
the genetic sequence).

"The use of high-dimensional statistical methods allowed us to study methylation in hundreds of thousands specific locations in the DNA at
the same time" says Arce Domingo-Relloso, MSc, data scientist and study co-author leading the statistical analyses for this project.

The researchers then took the same approach with four other major heart
disease cohorts: Atherosclerosis Risk in Communities (divided into
Black and white cohorts due to differences in timing and laboratory
methods), Framingham Heart Study, and Women's Health Initiative. In all,
they examined more than 400,000 DNA locations and 1,894 coronary heart
disease events.

In the initial analysis of Strong Heart data, they identified 506
epigenetic marks linked to cardiovascular risk. Of these, 33 were also
linked to cardiovascular risk in three or more of the other cohorts,
although some of these sites were associated with higher risk of disease
in one cohort but with lower risk of disease in other cohorts. Among the
33 methylation sites are those previously linked to cardiovascular risk
and smoking, as well as novel sites that the researchers say are worthy
of future investigation. Further analysis of the commonalities between
the 33 marks found that many of them are connected with EGFR gene,
which is involved in cell growth and cell survival.

"The overlap of these methylation sites across diverse cohorts supports
the idea of interconnected biological pathways for cardiovascular
risk," says Yuling Hong, MD, PhD, chief of the epidemiology branch
within the Division of Cardiovascular Sciences at the National Heart,
Lung, and Blood Institute. "The more we understand about early risk for cardiovascular disease the better we may be able to prevent illness, particularly in populations such as American Indians with relatively high
risk for heart disease." The study's senior author is Shelley A. Cole,
PhD, of the Texas Biomedical Research Institute. A full list of authors
is available on the journal's article page.

The Strong Heart Study was supported by grants for the National Heart,
Lung, and Blood Institute (NHLBI) (contract numbers: 75N92019D00027, 75N92019D00028, 75N92019D00029, 75N92019D00030) and previous grants
(HL090863, HL109315, HL109301, HL109284, HL109282, HL109319) and
cooperative agreements (HL41642, HL41652, HL41654, HL65520, HL65521)
and by the National Institute of Environmental Health Sciences (ES021367, ES025216, ES010349, ES009089). The Framingham Heart Study acknowledges the support of contracts NO1-HC-25195, HHSN268201500001I and 75N92019D00031
from the NHLBI and grant supplement HL092577-06S1 for this research. The Women's Health Initiative is funded by the NHLBI, National Institutes of
Health (NIH), and U.S. Department of Health and Human Services (HHS)
through contracts N268201600018C, N268201600001C, N268201600002C, N268201600003C, and N268201600004C. The Atherosclerosis Risk in
Communities study has been funded in whole or in part with funds from the NHLBI, NIH, HHS (contract numbers HHSN268201700001I, HHSN268201700002I, N268201700003I, N268201700004I, N268201700005I). Funding was also
supported by 5RC2HL102419 and NS087541. Investigator-specific funding is available on the journal's article page. Navas-Acien and several other
authors receive funding from the NHLBI and NIEHS.

========================================================================== Story Source: Materials provided by Columbia_University's_Mailman_School_of_Public_Health.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Ana Navas-Acien, Arce Domingo-Relloso, Pooja Subedi, Angela
L. Riffo-
Campos, Rui Xia, Lizbeth Gomez, Karin Haack, Jeff Goldsmith,
Barbara V.

Howard, Lyle G. Best, Richard Devereux, Ali Tauqeer, Ying Zhang,
Amanda M. Fretts, Gernot Pichler, Daniel Levy, Ramachandran
S. Vasan, Andrea A.

Baccarelli, Miguel Herreros-Martinez, Wan-yee Tang, Jan Bressler,
Myriam Fornage, Jason G. Umans, Maria Tellez-Plaza, M. Daniele
Fallin, Jinying Zhao, Shelley A. Cole. Blood DNA Methylation
and Incident Coronary Heart Disease. JAMA Cardiology, 2021; DOI:
10.1001/jamacardio.2021.2704 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210804123712.htm

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