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DNA methylation in the APOE genomic region is associated with cognitive function in African Americans

Overview of attention for article published in BMC Medical Genomics, May 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)
  • High Attention Score compared to outputs of the same age and source (96th percentile)

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Title
DNA methylation in the APOE genomic region is associated with cognitive function in African Americans
Published in
BMC Medical Genomics, May 2018
DOI 10.1186/s12920-018-0363-9
Pubmed ID
Authors

Jiaxuan Liu, Wei Zhao, Erin B. Ware, Stephen T. Turner, Thomas H. Mosley, Jennifer A. Smith

Abstract

Genetic variations in apolipoprotein E (APOE) and proximal genes (PVRL2, TOMM40, and APOC1) are associated with cognitive function and dementia, particularly Alzheimer's disease. Epigenetic mechanisms such as DNA methylation play a central role in the regulation of gene expression. Recent studies have found evidence that DNA methylation may contribute to the pathogenesis of dementia, but its association with cognitive function in populations without dementia remains unclear. We assessed DNA methylation levels of 48 CpG sites in the APOE genomic region in peripheral blood leukocytes collected from 289 African Americans (mean age = 67 years) from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Using linear regression, we examined the relationship between methylation in the APOE genomic region and multiple cognitive measures including learning, memory, processing speed, concentration, language and global cognitive function. We identified eight CpG sites in three genes (PVRL2, TOMM40, and APOE) that showed an inverse association between methylation level and delayed recall, a measure of memory, after adjusting for age and sex (False Discovery Rate q-value < 0.1). All eight CpGs are located in either CpG islands (CGIs) or CGI shelves, and six of them are in promoter regions. Education and APOE ε4 carrier status significantly modified the effect of methylation in cg08583001 (PVRL2) and cg22024783 (TOMM40), respectively. Together, methylation of the eight CpGs explained an additional 8.7% of the variance in delayed recall, after adjustment for age, sex, education, and APOE ε4 carrier status. Methylation was not significantly associated with any other cognitive measures. Our results suggest that methylation levels at multiple CpGs in the APOE genomic region are inversely associated with delayed recall during normal cognitive aging, even after accounting for known genetic predictors for cognition. Our findings highlight the important role of epigenetic mechanisms in influencing cognitive performance, and suggest that changes in blood methylation may be an early indicator of individuals at risk for dementia as well as potential targets for intervention in asymptomatic populations.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 87 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 87 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 15 17%
Student > Ph. D. Student 14 16%
Researcher 8 9%
Student > Doctoral Student 7 8%
Other 5 6%
Other 13 15%
Unknown 25 29%
Readers by discipline Count As %
Medicine and Dentistry 14 16%
Biochemistry, Genetics and Molecular Biology 11 13%
Neuroscience 11 13%
Psychology 8 9%
Agricultural and Biological Sciences 3 3%
Other 12 14%
Unknown 28 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 16. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 May 2019.
All research outputs
#2,249,299
of 24,973,800 outputs
Outputs from BMC Medical Genomics
#66
of 1,369 outputs
Outputs of similar age
#46,018
of 334,008 outputs
Outputs of similar age from BMC Medical Genomics
#2
of 25 outputs
Altmetric has tracked 24,973,800 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,369 research outputs from this source. They receive a mean Attention Score of 4.6. This one has done particularly well, scoring higher than 95% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 334,008 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 25 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.