Evidence map›Paper›PMID 29045054›Full record

ArticleGenes, brain, and behavior2018

Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease.

E E Blue, C-E Yu, T A Thornton, N H Chapman, E Kernfeld, N Jiang, K M Shively, K J Buckingham, C T Marvin, M J Bamshad and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genes, brain, and behavior, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 21% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. miRNA-576-5p promotes endometrial cancer cell growth and metastasis by targeting ZBTB4.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
  4. Inhibitors of DNA Methylation.Advances in experimental medicine and biology · 2022
    Review
  5. Review
  6. Article
  7. Local ancestry at APOE modifies Alzheimer's disease risk in Caribbean Hispanics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2019
    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

12 authors at 3 institutions in 1 country.

E E BlueDivision of Medical Genetics, University of Washington, Seattle, Washington.ORCID 0000-0002-0633-0305
C-E YuDivision of Gerontology, University of Washington, Seattle, Washington.
T A ThorntonDepartment of Biostatistics, University of Washington, Seattle, Washington.
N H ChapmanDivision of Medical Genetics, University of Washington, Seattle, Washington.
E KernfeldDepartment of Biostatistics, University of Washington, Seattle, Washington.
N JiangDepartment of Biology, University of Washington, Seattle, Washington.
K M ShivelyDepartment of Pediatrics, University of Washington, Seattle, Washington.
K J BuckinghamDepartment of Pediatrics, University of Washington, Seattle, Washington.
C T MarvinDepartment of Pediatrics, University of Washington, Seattle, Washington.
M J BamshadDepartment of Pediatrics, University of Washington, Seattle, Washington.
T D BirdDivision of Medical Genetics, University of Washington, Seattle, Washington.
E M WijsmanDivision of Medical Genetics, University of Washington, Seattle, Washington.ORCID 0000-0002-2725-6669
University of Washington · USUniversity of Washington Medical Center · USSeattle Children's Hospital · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Large Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7M
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
THE NIA GENETICS OF ALZHEIMER'S DISEASE DATA STORAGE SITEU24AG041689 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LI-SAN WANG · 2012 to 2026
$42.3M
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI DECARLI, CHARLES · 1991 to 2020
$28.3M
Building on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
Consortium for Alzheimers Sequence Analysis (CASA)UF1AG047133 · NIA · UNIVERSITY OF PENNSYLVANIA · PI FARRER, LINDSAY A., HAINES, JONATHAN L · 2014 to 2014
$12.6M
NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003079NHGRI NIH HHS U54 HG003273NHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS R01 HL105756NHLBI NIH HHS RC2 HL102419NIA NIH HHS P30 AG010129NIA NIH HHS P50 AG005136NIA NIH HHS R00 AG040184NIA NIH HHS R01 AG015473NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG041797NIA NIH HHS R01 AG059737NIA NIH HHS R37 AG015473NIA NIH HHS R56 AG051876NIA NIH HHS RF1 AG015473NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG049506NIA NIH HHS U01 AG049507NIA NIH HHS U01 AG049508NIA NIH HHS U01 AG052409NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG026395NIA NIH HHS U24 AG041689NIA NIH HHS UF1 AG047133NINDS NIH HHS R01 NS017950
6 · The paper itself

Abstract

The identification of novel genetic modifiers of age-at-onset (AAO) of Alzheimer's disease (AD) could advance our understanding of AD and provide novel therapeutic targets. A previous genome scan for modifiers of AAO among families affected by early-onset AD caused by the PSEN2 N141I variant identified 2 loci with significant evidence for linkage: 1q23.3 and 17p13.2. Here, we describe the fine-mapping of these 2 linkage regions, and test for replication in 6 independent datasets. By fine-mapping these linkage signals in a single large family, we reduced the linkage regions to 11% their original size and nominated 54 candidate variants. Among the 11 variants associated with AAO of AD in a larger sample of Germans from Russia, the strongest evidence implicated promoter variants influencing NCSTN on 1q23.3 and ZBTB4 on 17p13.2. The association between ZBTB4 and AAO of AD was replicated by multiple variants in independent, trans-ethnic datasets. Our results show association between AAO of AD and both ZBTB4 and NCSTN. ZBTB4 is a transcriptional repressor that regulates the cell cycle, including the apoptotic response to amyloid beta, while NCSTN is part of the gamma secretase complex, known to influence amyloid beta production. These genes therefore suggest important roles for amyloid beta and cell cycle pathways in AAO of AD.

Indexed as

AgedAged, 80 and overAge of OnsetAlzheimer DiseaseAmyloid Precursor Protein SecretasesChromosome MappingFemaleGenetic LinkageGenetic Predisposition to DiseaseGenetic VariationGenotypeHumansMaleMembrane GlycoproteinsPromoter Regions, GeneticRepressor ProteinsAmyloid Precursor Protein SecretasesMembrane Glycoproteinsnicastrin proteinRepressor ProteinsZBTB4 protein, humanage-at-onsetamyloid betaapoptotic responseassociationcomplex traitsdementiafine-mappinggenetic modifierslinkage analysisnoncoding variantssurvival analysis

Identifiers

PMID29045054
PMCPMC5902667
OpenAlexW2767069411

What OpenQuestion holds

Textmetadata
LicenceTDM
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.