Evidence map›Paper›PMID 39711484›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Examination of MGMT as a risk gene for dementia in the Amish.

Leighanne R Main, Yeunjoo E Song, Audrey Lynn, Renee A Laux, Kristy L Miskimen, Michael D Osterman, Michael L Cuccaro, Paula K Ogrocki, Alan J Lerner, Jeffery M Vance and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Examination of MGMT as a risk gene for dementia in the Amish.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    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

22 authors.

Leighanne R MainDepartments of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
Yeunjoo E SongDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Audrey LynnDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Renee A LauxDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Kristy L MiskimenDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Michael D OstermanDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Michael L CuccaroJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Paula K OgrockiDepartment of Neurology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Alan J LernerDepartment of Neurology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Jeffery M VanceJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
M Denise FuzzellDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Sarada L FuzzellDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Sherri D HochstetlerDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Daniel A DorfsmanJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Laura J CaywoodJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Michael B ProughJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Larry D AdamsJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Jason E ClouseJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Sharlene D HeringtonJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
William K ScottJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Jonathan L HainesDepartments of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, USA.

Funding

The Alzheimer Disease Sequence Analysis CollaborativeU01AG058654 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI BUSH, WILLIAM S, FARRER, LINDSAY A. · 2018 to 2022
$14.6M
Protective Genetic Varients for Alzheimer Disease in the AmishR01AG058066 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI Jonathan L Haines, Margaret A. Pericak-Vance · 2022 to 2026
$8.0M
The Alzheimer's Disease Translational Data Science Training ProgramT32AG071474 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI BUSH, WILLIAM S · 2021 to 2025
$1.1M
NIA NIH HHS R01 AG058066NIA NIH HHS T32 AG071474NIA NIH HHS U01 AG058654NIH HHS
6 · The paper itself

Abstract

introductionRecently, the O-6-methylguanine-DNA methyltransferase (MGMT) locus was proposed as influencing the risk of Alzheimer's disease (AD) in women who did not carry the apolipoprotein E ε4 allele. We examined an Amish founder population for any influence of genetic variation in and around the MGMT locus on the risk for dementia.

methodsGenetic association was performed for single nucleotide polymorphisms (SNPs) surrounding the MGMT locus. A total of 946 individuals of Amish descent between the ages of 76 and 95 who were classified as cognitively impaired or cognitively unimpaired were included. Multiple statistical models were applied to test for replication.

resultsThe results for the previously associated individual SNPs were not significant. However, a different SNP (rs7909468) generated significant results under a model different from the previous report. DISCUSSION: The MGMT locus may influence the risk of AD, although its genetic mechanisms remain unclear and warrant further study. HIGHLIGHTS: Association analyses around the O-6-methylguanine-DNA methyltransferase (MGMT) locus showed a study-significant single nucleotide polymorphism (SNP), rs7909468, in a female cognitively impaired group lacking the apolipoprotein E ε4 genotype. Functional implications of rs7909468 are relatively unexplored, but in silico analyses indicate it may regulate MGMT expression. rs7909468 was not in linkage disequilibrium with other SNPs found to be significant in this region and appears as a distinct novel association.

Indexed as

DementiaDNA Modification MethylasesDNA Repair EnzymesGenetic Predisposition to DiseasePolymorphism, Single NucleotideTumor Suppressor ProteinsAgedAged, 80 and overFemaleGenetic Association StudiesGenotypeHumansMaleDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanTumor Suppressor ProteinsAlzheimer's diseasecognitive impairmentgenetic associationisolated founder populationpedigree study

Identifiers

PMID39711484
PMCPMC11782184

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.