Evidence map›Paper›PMID 29739406›Full record

ArticleBMC medical genomics2018

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

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

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medical genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 43 citations in OpenAlex.

  1. Trial
  2. Article
  3. Exploring potential mechanisms of an African protective locus for Alzheimer's disease in APOEε4 carriers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  4. Review
  5. Review
  6. Genome-wide methylomic regulation of multiscale gene networks in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Superior Frontal GyrusJournal of Alzheimer's disease reports · 2021
    Article
  12. Observational
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Jiaxuan LiuDepartment of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, 4602 SPH Tower, Ann Arbor, MI, 48109-2029, USA.
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, 4602 SPH Tower, Ann Arbor, MI, 48109-2029, USA.
Erin B WareSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
Stephen T TurnerDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, 55905, USA.
Thomas H MosleyDepartment of Neurology, University of Mississippi Medical Center, Jackson, MS, 39126, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, 4602 SPH Tower, Ann Arbor, MI, 48109-2029, USA. smjenn@umich.edu.
University of Michigan–Ann Arbor · USJackson Memorial Hospital · USMayo Clinic · US

Funding

Genetics of Microangiopathic Brain InjuryR01NS041558 · NINDS · MAYO CLINIC ROCHESTER · PI TURNER, STEPHEN T · 2001 to 2010
$5.8M
GENETIC DETERMINANTS OF HIGH BP IN THREE RACIAL GROUPSU01HL054457 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KARDIA, SHARON L · 2000 to 2004
$2.8M
Epigenetics of Arteriosclerosis in African American Hypertensive SibshipsR01HL133221 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SMITH, JENNIFER ANN · 2016 to 2019
$2.2M
Genetic Mechanisms of Arteriosclerosis in Hypertensive SibshipsR01HL119443 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KARDIA, SHARON L · 2014 to 2017
$2.1M
Epigenetic Biomarkers of Common Chronic DiseasesRC1HL100185 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KARDIA, SHARON L · 2009 to 2010
$999k
GENETIC DETERMINANTS OF HIGH BP IN THREE RACIAL GROUPSU10HL054457 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SING, CHARLES F · 1995 to 1999
–
NHLBI NIH HHS HL054457NHLBI NIH HHS HL100185NHLBI NIH HHS HL119443NHLBI NIH HHS HL133221NHLBI NIH HHS R01 HL119443NHLBI NIH HHS R01 HL133221NHLBI NIH HHS RC1 HL100185NHLBI NIH HHS U01 HL054457NHLBI NIH HHS U10 HL054457NINDS NIH HHS NS041558NINDS NIH HHS R01 NS041558
6 · The paper itself

Abstract

backgroundGenetic 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.

methodsWe 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.

resultsWe 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.

conclusionsOur 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.

Indexed as

CognitionDNA MethylationGenomicsAgedAged, 80 and overApolipoprotein C-IApolipoproteins EBlack or African AmericanBrainCpG IslandsEducational StatusFemaleGenotypeHumansMaleMembrane Transport ProteinsAPOC1 protein, humanApolipoprotein C-IApolipoproteins EMembrane Transport ProteinsMitochondrial Precursor Protein Import Complex ProteinsNECTIN2 protein, humanNectinsTOMM40 protein, humanApolipoprotein ECognitionCognitive functionDelayed recallDNA methylationEpigeneticsMemory

Identifiers

PMID29739406
PMCPMC5941603
OpenAlexW2803820237

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.