An epigenetic predictor of death captures multi-modal measures of brain health.
An epigenetic predictor of death captures multi-modal measures of brain health.
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DOI：
10.1038/s41380-019-0616-9
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发表时间：
2021-08
影响因子：
11
通讯作者：
Marioni RE
中科院分区：
文献类型：
--
作者：
Hillary RF;Stevenson AJ;Cox SR;McCartney DL;Harris SE;Seeboth A;Higham J;Sproul D;Taylor AM;Redmond P;Corley J;Pattie A;Hernández MDCV;Muñoz-Maniega S;Bastin ME;Wardlaw JM;Horvath S;Ritchie CW;Spires-Jones TL;McIntosh AM;Evans KL;Deary IJ;Marioni RE
相同实足年龄的个体表现出不同的生物衰老速度。因此，已经提出了许多方法来确定生物学年龄，并主要利用DNA甲基化水平（DNAm）的变化。一种名为“DNAm GrimAge”的新型表观遗传时钟在预测死亡风险以及许多与年龄相关的疾病方面优于其前辈。然而，DNAm GrimAge和认知或神经影像表型之间的关联仍然未知。我们探讨这些协会在洛锡安出生队列1936年（n = 709，平均年龄73岁）。较高的DNA GrimAge与80年代的全因死亡率密切相关（GrimAge每标准差增加的风险比：1.81，P < 2.0 × 10−16）。较高的DNAm GrimAge与11岁时较低的智商（β =-0.11）、73岁时较低的一般认知能力（β =-0.18）、脑体积减小（β =-0.25）和脑白色高信号增加（β = 0.17）相关。有初步证据表明，从70岁到79岁，DNAm GrimAge和认知能力下降之间存在纵向关联。在137个健康和大脑相关的表型中，有69个与GrimAge显著相关。调整所有模型的儿童智力衰减到非显着性的一小部分协会（12/69协会，其中6个是认知特征），但不是与一般认知能力（衰减33.9%）。较高的DNAm GrimAge与老年人较低的认知能力和脑血管病变相关，独立于早期的认知能力。这种死亡率的表观遗传预测因子与大脑健康的不同衡量标准有关，可能有助于预测与年龄相关的认知能力下降。
Individuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed ‘DNAm GrimAge’ has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10−16). Higher DNAm GrimAge was associated with lower age 11 IQ (β = −0.11), lower age 73 general cognitive ability (β = −0.18), decreased brain volume (β = −0.25) and increased brain white matter hyperintensities (β = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.
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DOI：
10.1136/bmj.c3666
发表时间：
2010-07-26
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Debette S;Markus HS
通讯作者：
Markus HS
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
4.1
作者：
Deary IJ;Gow AJ;Taylor MD;Corley J;Brett C;Wilson V;Campbell H;Whalley LJ;Visscher PM;Porteous DJ;Starr JM
通讯作者：
Starr JM
影响因子：
11
作者：
Karama, S.;Bastin, M. E.;Murray, C.;Royle, N. A.;Penke, L.;Munoz Maniega, S.;Gow, A. J.;Corley, J.;Hernandez, Mdelc Valdes;Lewis, J. D.;Rousseau, M-E;Lepage, C.;Fonov, V.;Collins, D. L.;Booth, T.;Rioux, P.;Sherif, T.;Adalat, R.;Starr, J. M.;Evans, A. C.;Wardlaw, J. M.;Deary, I. J.
通讯作者：
Deary, I. J.
影响因子：
3.7
作者：
Kadoglou, Nikolaos P. E.;Biddulph, Jane P.;Demakakos, Panayotes
通讯作者：
Demakakos, Panayotes