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Epigenetic age acceleration in adolescence associates with BMI, inflammation and risk score for middle age cardiovascular disease

Epigenetic age acceleration in adolescence associates with BMI, inflammation and risk score for middle age cardiovascular disease
Epigenetic age acceleration in adolescence associates with BMI, inflammation and risk score for middle age cardiovascular disease
Background

‘Accelerated ageing’, assessed by adult DNA methylation predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age 17-years) associated with adiposity/CVD-risk measured (ages 17, 20, 22-years), and projected CVD by middle-age.
Methods

DNA methylation measured in peripheral blood provided 2 estimates of epigenetic age acceleration; intrinsic (IEAA, (preserved across cell types) and extrinsic (EEAA, dependent on cell admixture and methylation levels within each cell type).

Adiposity was assessed by anthropometry, ultrasound and DEXA (ages 17, 20, 22 years). CVD-risk factors (lipids, HOMA-IR, blood pressure, inflammatory markers) were assessed at age 17-years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients/5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD-risk factors and CVD development.
Results

In 995 participants (49.6% female, age 17.3+/-0.6 years), EEAA (/5-years) was associated with increased BMI of 2.4% (95%CI 1.2-3.6%) and 2.4% (0.8-3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3-33%) in hsCRP, 10% (4-17%) in interferon-gamma induced protein (IP-10) and 4% (2-6%) in tumour necrosis factor receptor 2 (sTNFR2), adjusted for BMI and HOMA-IR. EEAA(/5-years) results in a 4% increase in hard endpoints of CVD by 47 years old and a 3% increase, after adjustment for conventional risk factors.
Conclusions

Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle-age CVD. Irrespective whether this is cause or effect, assessing epigenetic age might refine disease prediction.
0021-972X
Huang, R.C.
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Lillycrop, K.A.
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Beilin, L.J.
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Godfrey, K.M.
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Anderson, D.
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Mori, T.A.
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Rauschert, S.
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Craig, J.M.
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Oddy, W.H.
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Ayonrinde, O.T.
25789c5f-d3d6-438d-8aa8-e3577df5c0df
Pennell, C.E.
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Holbrook, J.D.
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Melton, P.E.
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Huang, R.C.
d39aca4d-8017-48c3-8f40-0aa2e52dbf66
Lillycrop, K.A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Beilin, L.J.
7728e5b8-3049-4273-bb16-d4f95088d91a
Godfrey, K.M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Anderson, D.
441a2220-b721-417d-b9f4-8f40ed17a621
Mori, T.A.
182e02e5-0b4a-44c2-81c6-f910c7a4d0e6
Rauschert, S.
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Craig, J.M.
34883fb4-710b-4ee4-8a43-2a53ed92b825
Oddy, W.H.
1117306e-e383-424f-8525-13b0e493a2e7
Ayonrinde, O.T.
25789c5f-d3d6-438d-8aa8-e3577df5c0df
Pennell, C.E.
80d0fd73-56a9-46fe-84d3-d0e693cdb042
Holbrook, J.D.
69989b79-2710-4f12-946e-c6214e1b6513
Melton, P.E.
0d57b167-a10c-4b22-83da-b983f378966f

Huang, R.C., Lillycrop, K.A., Beilin, L.J., Godfrey, K.M., Anderson, D., Mori, T.A., Rauschert, S., Craig, J.M., Oddy, W.H., Ayonrinde, O.T., Pennell, C.E., Holbrook, J.D. and Melton, P.E. (2019) Epigenetic age acceleration in adolescence associates with BMI, inflammation and risk score for middle age cardiovascular disease. Journal of Clinical Endocrinology & Metabolism. (doi:10.1210/jc.2018-02076).

Record type: Article

Abstract

Background

‘Accelerated ageing’, assessed by adult DNA methylation predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age 17-years) associated with adiposity/CVD-risk measured (ages 17, 20, 22-years), and projected CVD by middle-age.
Methods

DNA methylation measured in peripheral blood provided 2 estimates of epigenetic age acceleration; intrinsic (IEAA, (preserved across cell types) and extrinsic (EEAA, dependent on cell admixture and methylation levels within each cell type).

Adiposity was assessed by anthropometry, ultrasound and DEXA (ages 17, 20, 22 years). CVD-risk factors (lipids, HOMA-IR, blood pressure, inflammatory markers) were assessed at age 17-years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients/5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD-risk factors and CVD development.
Results

In 995 participants (49.6% female, age 17.3+/-0.6 years), EEAA (/5-years) was associated with increased BMI of 2.4% (95%CI 1.2-3.6%) and 2.4% (0.8-3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3-33%) in hsCRP, 10% (4-17%) in interferon-gamma induced protein (IP-10) and 4% (2-6%) in tumour necrosis factor receptor 2 (sTNFR2), adjusted for BMI and HOMA-IR. EEAA(/5-years) results in a 4% increase in hard endpoints of CVD by 47 years old and a 3% increase, after adjustment for conventional risk factors.
Conclusions

Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle-age CVD. Irrespective whether this is cause or effect, assessing epigenetic age might refine disease prediction.

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Accepted/In Press date: 15 February 2019
e-pub ahead of print date: 20 February 2019

Identifiers

Local EPrints ID: 428555
URI: https://eprints.soton.ac.uk/id/eprint/428555
ISSN: 0021-972X
PURE UUID: 7dfc69e0-7372-420e-a4b8-2fd932f4f9b3
ORCID for K.A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for K.M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for J.D. Holbrook: ORCID iD orcid.org/0000-0003-1791-6894

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Date deposited: 01 Mar 2019 17:30
Last modified: 14 Mar 2019 01:54

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