Evidence map›Paper›PMID 34852950›Full record

ArticleNeurobiology of aging2022

Association between WWOX/MAF variants and dementia-related neuropathologic endophenotypes.

Adam J Dugan, Peter T Nelson, Yuriko Katsumata, Lincoln M P Shade, Merilee A Teylan, Kevin L Boehme, Shubhabrata Mukherjee, John S K Kauwe, Timothy J Hohman, Julie A Schneider and 2 more

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

Article in Neurobiology of aging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 16% 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.

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3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 14 citations in OpenAlex.

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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 5 institutions in 1 country.

Adam J DuganDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA.
Peter T NelsonSanders-Brown Center on Aging and Alzheimer's Disease Research Center, University of Kentucky, Lexington, KY, USA; Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY, USA.
Yuriko KatsumataDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging and Alzheimer's Disease Research Center, University of Kentucky, Lexington, KY, USA.
Lincoln M P ShadeDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA.
Merilee A TeylanNational Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA.
Kevin L BoehmeDepartment of Biology, Brigham Young University, Provo, UT, USA.
Shubhabrata MukherjeeDepartment of Medicine, University of Washington, Seattle, WA, USA.
John S K KauweDepartment of Biology, Brigham Young University, Provo, UT, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
Timothy J HohmanVanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Julie A SchneiderDepartments of Neurology and Pathology, Rush University Medical Center, Chicago, IL, USA.
David W FardoDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging and Alzheimer's Disease Research Center, University of Kentucky, Lexington, KY, USA. Electronic address: david.fardo@uky.edu.
Alzheimer's Disease Genetics Consortium
University of Kentucky · USBrigham Young University · USUniversity of Washington · USRush University Medical Center · USVanderbilt University Medical Center · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
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
TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
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
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GALASKO, DOUGLAS R · 1985 to 2018
$55.4M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
NCATS NIH HHS TL1 TR001997NCI NIH HHS R01 CA129769NCRR NIH HHS UL1 RR029893NHGRI NIH HHS U01 HG004610NHGRI NIH HHS U01 HG006375NIA NIH HHS K01 AG049164NIA NIH HHS K08 AG065463NIA NIH HHS K25 AG055620NIA NIH HHS P01 AG002219NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG010491NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG008051NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG012300NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG028377NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG035982NIA NIH HHS P30 AG049638NIA NIH HHS P30 AG053760NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062428NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072977NIA NIH HHS P50 AG005128NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005134NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG005144NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008671NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG016582NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG033514NIA NIH HHS P50 AG047266NIA NIH HHS P50 AG047270NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG012101NIA NIH HHS R01 AG013616NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017173NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG019757NIA NIH HHS R01 AG020688NIA NIH HHS R01 AG021547NIA NIH HHS R01 AG022374NIA NIH HHS R01 AG025259NIA NIH HHS R01 AG026916NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG031581NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG035137NIA NIH HHS R01 AG041232NIA NIH HHS R01 AG041718NIA NIH HHS R01 AG041797NIA NIH HHS R01 AG057187NIA NIH HHS R01 AG059716NIA NIH HHS R01 AG061518NIA NIH HHS R01 AG067482NIA NIH HHS R21 AG061551NIA NIH HHS R37 AG015473NIA NIH HHS R56 AG057191NIA NIH HHS RC2 AG036502NIA NIH HHS RC2 AG036528NIA NIH HHS T32 AG057461NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG026395NIA NIH HHS U24 AG041689NIMH NIH HHS P50 MH060451NIMH NIH HHS R01 MH080295NINDS NIH HHS P50 NS039764NINDS NIH HHS R01 NS059873Wellcome Trust
6 · The paper itself

Abstract

The genetic locus containing the WWOX and MAF genes was implicated as a clinical Alzheimer's disease (AD) risk locus in two recent large meta-analytic genome wide association studies (GWAS). In a prior GWAS, we identified a variant in WWOX as a suggestive risk allele for hippocampal sclerosis. We hypothesized that the WWOX/MAF locus may be preferentially associated with non-plaque- and non-tau-related neuropathological changes (NC). Data from research participants with GWAS and autopsy measures from the National Alzheimer's Coordinating Center and the Religious Orders Study and the Rush Memory and Aging Project were meta-analyzed. Notably, no variants in the locus were significantly associated with ADNC. However, several WWOX/MAF variants had significant adjusted associations with limbic-predominant age-related TDP-43 encephalopathy NC (LATE-NC), HS, and brain arteriolosclerosis. These associations remained largely unchanged after adjustment for ADNC (operationalized with standard semiquantitative staging), suggesting that these associations are independent of ADNC. Thus, WWOX genetic variants were associated pathologically with LATE-NC, not ADNC.

Indexed as

PhenotypeAgedAged, 80 and overAlzheimer DiseaseDementiaFemaleGenetic VariationGenome-Wide Association StudyHumansMaleProto-Oncogene Proteins c-mafTDP-43 ProteinopathiesTumor Suppressor ProteinsWW Domain-Containing OxidoreductaseMAF protein, humanProto-Oncogene Proteins c-mafTumor Suppressor ProteinsWW Domain-Containing OxidoreductaseWWOX protein, humanADNCADRDHippocampusHumanSNPSNV

Identifiers

PMID34852950
PMCPMC8761217
OpenAlexW3208157266

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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 OpenQuestion graph.