4.8 Article

An epigenetic predictor of death captures multi-modal measures of brain health

期刊

MOLECULAR PSYCHIATRY
卷 26, 期 8, 页码 3806-3816

出版社

SPRINGERNATURE
DOI: 10.1038/s41380-019-0616-9

关键词

-

资金

  1. Age UK as The Disconnected Mind project [LBC1936]
  2. Medical Research Council [G0701120, G1001245, MR/M013111/1, MR/R024065/1]
  3. National Institutes of Health (NIH) [R01AG054628]
  4. Wellcome Trust [108890/Z/15/Z]
  5. University of Edinburgh College of Medicine and Veterinary Medicine
  6. Alzheimer's Research UK [ARUK-PG2017B-10]
  7. Fondation Leducq
  8. [1U01AG060908 -01]
  9. MRC [UKDRI-4004, G0701120, MR/R024065/1, G1001245, MR/M013111/1] Funding Source: UKRI

向作者/读者索取更多资源

The study found that higher DNAm GrimAge is associated with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability.
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 x 10(-16)). Higher DNAm GrimAge was associated with lower age 11 IQ (beta = -0.11), lower age 73 general cognitive ability (beta = -0.18), decreased brain volume (beta = -0.25) and increased brain white matter hyperintensities (beta = 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据