Evidence map›Paper›PMID 39376159›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.

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, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. 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. Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  5. Article
4 · The record

Corrections and comments

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.ORCID 0000-0002-8828-8066
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.
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

Protective Genetic Variants for Alzheimer Disease in the AmishRF1AG058066 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI HAINES, JONATHAN L, PERICAK-VANCE, MARGARET A. · 2017 to 2019
$8.2M
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
Alzheimer's Disease Translational Data Science Training 5T32AG071474-02NIA NIH HHS AG058066NIA NIH HHS R01 AG058066NIA NIH HHS RF1 AG058066NIA NIH HHS T32 AG071474NIH HHS
6 · The paper itself

Abstract

introductionAlzheimer's disease (AD) remains a debilitating condition with limited treatments and additional therapeutic targets needed. Identifying AD protective genetic loci may identify new targets and accelerate identification of therapeutic treatments. We examined a founder population to identify loci associated with cognitive preservation into advanced age.

methodsGenome-wide association and linkage analyses were performed on 946 examined and sampled Amish individuals, aged 76-95, who were either cognitively unimpaired (CU) or impaired (CI).

resultsA total of 12 single nucleotide polymorphisms (SNPs) demonstrated suggestive association (P ≤ 5 × 10 DISCUSSION: A novel significant result for cognitive preservation on chromosome 2 includes the genes LRRTM4 and CTNNA2. Additionally, the lead SNP, rs1402906, impacts the POU3F2 transcription factor binding affinity, which regulates LRRTM4 and CTNNA2. HIGHLIGHTS: GWAS and linkage identified over 100 loci associated with cognitive preservation. One locus on Chromosome 2 retained significance over multiple analyses. Predicted TFBSs near rs1402906 regulate genes associated with neurocognition.

Indexed as

AmishChromosomes, Human, Pair 2Genome-Wide Association StudyPolymorphism, Single NucleotideAgedAged, 80 and overAlzheimer DiseaseCognitionCognitive DysfunctionFemaleGenetic LinkageHumansMaleAlzheimer diseasecognitive preservationcognitive resiliencecognitive resistanceGWASisolated founder populationlinkage

Identifiers

PMID39376159
PMCPMC11567819

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.