Association of DNA methylation in the brain with age in older persons is confounded by common neuropathologies.
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Abstract | DNA methylation plays a crucial role in the regulation of gene expression, cell differentiation and development. Previous studies have reported age-related alterations of methylation levels in the human brain across the lifespan, but little is known about whether the observed association with age is confounded by common neuropathologies among older persons. Using genome-wide DNA methylation data from 740 postmortem brains, we interrogated 420,132 CpG sites across the genome in a cohort of individuals with ages from 66 to 108 years old, a range of ages at which many neuropathologic indices become quite common. We compared the association of DNA methylation prior to and following adjustment for common neuropathologies using a series of linear regression models. In the simplest model adjusting for technical factors including batch effect and bisulfite conversion rate, we found 8156 CpGs associated with age. The number of CpGs associated with age dropped by more than 10% following adjustment for sex. Notably, after adjusting for common neuropathologies, the total number of CpGs associated with age was reduced by approximately 40%, compared to the sex-adjusted model. These data illustrate that the association of methylation changes in the brain with age is inflated if one does not account for age-related brain pathologies. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease. |
Year of Publication | 2015
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Journal | Int J Biochem Cell Biol
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Volume | 67
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Pages | 58-64
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Date Published | 2015 Oct
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ISSN | 1878-5875
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URL | |
DOI | 10.1016/j.biocel.2015.05.009
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PubMed ID | 26003740
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PubMed Central ID | PMC4564337
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Grant list | U01 AG046152 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
K25 AG041906 / AG / NIA NIH HHS / United States
R01AG36042 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01AG17917 / AG / NIA NIH HHS / United States
U01AG46152 / AG / NIA NIH HHS / United States
R01 AG036042 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01AG15819 / AG / NIA NIH HHS / United States
P30AG10161 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States
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