Evidence map›Paper›PMID 41253753›Full record

ArticleTranslational psychiatry2025

Monocyte inflammation and resilience to Alzheimer's disease: novel genetic risk genes identified by transcriptome-wide association study.

Yousef Mustafa, Leighanne R Main, Makaela Mews, Vaibhav A Janve, Timothy J Hohman, Jonathan L Haines, Yeunjoo E Song, Anthony J Griswold, Margaret A Pericak-Vance, William K Scott and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

14 authors.

Yousef MustafaCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA. yim2@case.edu.ORCID http://orcid.org/0000-0002-5935-7069
Leighanne R MainCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Makaela MewsCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Vaibhav A JanveVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Timothy J HohmanVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-3377-7014
Jonathan L HainesCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Yeunjoo E SongDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Anthony J GriswoldJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA and The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA and The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
William K ScottJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA and The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.ORCID http://orcid.org/0000-0001-9336-6404
Adam C NajDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Jennifer E BelowVanderbilt Genetics Institute and Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Logan DumitrescuVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
William S BushCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA. wsb36@case.edu.ORCID http://orcid.org/0000-0002-9729-6519

Funding

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
Genetic Drivers of Resilience to Alzheimer's DiseaseR01AG059716 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HOHMAN, TIMOTHY J · 2018 to 2022
$4.4M
Functional genetic analyses of existing data resources to expand AD gene discoveryRF1AG061351 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BELOW, JENNIFER, BUSH, WILLIAM S · 2019 to 2019
$3.0M
Genomic, Epigenomic, and Transcriptomic Mechanisms of Contributing to Alzheimer's Disease Risk in Diverse Ancestral PopulationsRF1AG070935 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BUSH, WILLIAM S, GRISWOLD, ANTHONY JOHN · 2021 to 2021
$2.3M
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 R01 AG059716NIA NIH HHS RF1 AG061351NIA NIH HHS RF1 AG070935NIA NIH HHS T32 AG071474U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) RF1AG070935
6 · The paper itself

Abstract

Inflammation is a key driver of Alzheimer's disease (AD) and may connect all known AD risk factors. Recently, AD resilience outcomes have been developed which have helped to uncover mechanisms that enable some individuals to withstand significant AD pathology or genetic risk, while retaining cognitive function. We conducted a series of transcriptome-wide association studies (TWAS) focusing on monocytes, key innate immune cells that respond to pathogens and invade the CNS. Monocyte expression data under various immune stimulation states (naive, LPS 2 h, LPS 24 h, IFN 24 h) and corresponding genotype data from 432 individuals (Fairfax et al. [1]) were analyzed. We developed cis-genetic expression models using both elastic-net, and MASH combined with LD-pruning; capturing polygenic structures and independent inflammatory eQTLs across conditions, respectively. These models were applied to GWAS summary statistics of three AD resilience phenotypes: cognitive and global AD-resilience, and Amish cognitive preservation. We identified 180 TWAS results surpassing a suggestive significance threshold of P

Indexed as

Alzheimer DiseaseInflammationMonocytesResilience, PsychologicalAgedFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleTranscriptome

Identifiers

PMID41253753
PMCPMC12627486

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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.