Evidence map›Paper›PMID 38460116›Full record

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

Genetic associations with dementia-related proteinopathy: Application of item response theory.

Yuriko Katsumata, David W Fardo, Lincoln M P Shade, Xian Wu, Shama D Karanth, Timothy J Hohman, Julie A Schneider, David A Bennett, Jose M Farfel, Kathryn Gauthreaux and 6 more

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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 7 papers.

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0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. NIAGADS: A data repository for Alzheimer's disease and related dementia genomics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  5. Article
  6. Review
  7. Genetic associations with dementia-related proteinopathy: Application of item response theory.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    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

16 authors.

Yuriko KatsumataDepartment of Biostatistics, University of Kentucky, Lexington, Kentucky, USA.
David W FardoDepartment of Biostatistics, University of Kentucky, Lexington, Kentucky, USA.
Lincoln M P ShadeDepartment of Biostatistics, University of Kentucky, Lexington, Kentucky, USA.
Xian WuDepartment of Biostatistics, University of Kentucky, Lexington, Kentucky, USA.
Shama D KaranthDepartment of Surgery, College of Medicine, University of Florida, Gainesville, Florida, USA.
Timothy J HohmanVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Julie A SchneiderDepartment of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
David A BennettDepartment of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Jose M FarfelDepartment of Pathology, Rush University Medical Center, Chicago, Illinois, USA.
Kathryn GauthreauxNational Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Charles MockNational Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Walter A KukullNational Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Erin L AbnerSanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
Peter T NelsonSanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
Alzheimer's Disease Neuroimaging InitiativeDepartment of Radiology, Northern California Institute for Research and Education (NCIRE), San Francisco, California, USA.
National Alzheimer's Coordinating Center

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
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MONICA G. RIVERA-MINDT · 2016 to 2026
$226.7M
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
VCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7M
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
Alzheimer's AssociationEuropean Research Council 340755NHGRI NIH HHS RC2 HG005605NHGRI NIH HHS U01 HG004610NHGRI NIH HHS U01 HG006375NHGRI NIH HHS U01 HG008657NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003079NHGRI NIH HHS U54 HG003273NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 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HHS R01 AG009956NIA NIH HHS R01 AG011101NIA NIH HHS R01 AG011380NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG015928NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG017919NIA NIH HHS R01 AG018016NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG019757NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG021136NIA NIH HHS R01 AG021547NIA NIH HHS R01 AG023629NIA NIH HHS R01AG023629NIA NIH HHS R01 AG025259NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG028786NIA NIH HHS R01 AG031272NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG033040NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG038651NIA NIH HHS R01 AG041797NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG057187NIA NIH HHS R01AG057187NIA NIH HHS R01 AG079280NIA NIH HHS R01 AG082730NIA NIH HHS R01AG082730NIA NIH HHS R01s AG054076NIA NIH HHS R37 AG015473NIA NIH HHS R56 AG051876NIA NIH HHS RC2 AG036528NIA NIH HHS RC4 AG039085NIA NIH HHS RF1 AG015473NIA NIH HHS RF1 AG051504NIA NIH HHS RF1 AG054023NIA NIH HHS RF1 AG054052NIA NIH HHS RF1 AG054074NIA NIH HHS RF1 AG057519NIA NIH HHS RF1 AG058066NIA NIH HHS RF1 AG058267NIA NIH HHS RF1 AG082339NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG049506NIA NIH HHS U01 AG049507NIA NIH HHS U01 AG049508NIA NIH HHS U01 AG052409NIA NIH HHS U01 AG052410NIA NIH HHS U01 AG052411NIA NIH HHS U01 AG057659NIA NIH HHS U01 AG058589NIA NIH HHS U01 AG058635NIA NIH HHS U01 AG058654NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG062602NIA NIH HHS U01 AG062943NIA NIH HHS U19 AG024904NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24AG07122NIA NIH HHS U24 AG072122NIA NIH HHS U54 AG052427NIA NIH HHS UF1 AG047133NINDS NIH HHS F30 NS124136NINDS NIH HHS P01 NS026630NINDS NIH HHS P50 NS039764NINDS NIH HHS P50 NS071674NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS029993NINDS NIH HHS R01 NS069719NINDS NIH HHS R01NS069719NINDS NIH HHS R01 NS080820NINDS NIH HHS U01 NS041588Wellcome TrustWellcome Trust GR066133/GR080002
6 · The paper itself

Abstract

introductionAlthough dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.

methodsWe applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43.

resultsFinal included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility. DISCUSSION: A novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies. HIGHLIGHTS: Latent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors.

Indexed as

Alzheimer DiseaseBiological ProductsDementiaProteostasis DeficienciesTDP-43 Proteinopathiesalpha-SynucleinDNA-Binding ProteinsHumansMembrane ProteinsNerve Tissue Proteinsalpha-SynucleinBiological ProductsDNA-Binding ProteinsMembrane ProteinsNerve Tissue ProteinsTMEM106B protein, humanAlzheimer's Coordinating CenterAlzheimer's Disease Neuroimaging InitiativeAlzheimer's disease neuropathologic changes (ADNC)Alzheimer's Disease Sequencing ProjectARHGEF28Item response theoryLewyneuropathologyReligious Orders StudyRGNEFRush Memory and Aging Project (MAP)SDHAF1TMEM68

Identifiers

PMID38460116
PMCPMC11032554

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