Evidence map›Paper›PMID 41231230›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Integrative multi-omics approaches identify molecular pathways and improve Alzheimer's disease risk prediction.

Rasika Venkatesh, Katie M Cardone, Yuki Bradford, Anni K Moore, Rachit Kumar, Jason H Moore, Li Shen, Dokyoon Kim, Marylyn D Ritchie

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. 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
–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. Observational
  2. Review
  3. Review
  4. Genetic Burden andJournal of personalized medicine · 2026
    Article
  5. Review
  6. Designing Neural Dynamics: From Digital Twin Modeling to Regeneration.International journal of molecular sciences · 2025
    Review
  7. Integrative multi-omics approaches identify molecular pathways and improve Alzheimer's disease risk prediction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Rasika VenkateshGenomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0009-0003-4471-4291
Katie M CardoneInstitute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Yuki BradfordInstitute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Anni K MooreGenomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Rachit KumarGenomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jason H MooreDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Li ShenInstitute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Dokyoon KimInstitute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Marylyn D RitchieInstitute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-1208-1720

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
The Alzheimer's Clinical Trial Consortium - Down Syndrome Network (ACTC- DSN)U24AG057437 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Paul S. Aisen, RONALD C PETERSEN · 2018 to 2026
$198.4M
The Health & Aging Brain Study - Health Disparities (HABS-HD)U19AG078109 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI LEIGH A JOHNSON · 2022 to 2026
$181.1M
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
RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
Translational pharmacoepidemiology: neuroprotection and neurotoxicity of antihypertensives and strong anticholinergicsU19AG066567 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI Christine L MacDonald · 2021 to 2026
$80.4M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
NHGRI NIH HHS RC2 HG005605NHGRI NIH HHS T32 HG000046NHGRI NIH HHS T32HG000046NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003079NHGRI NIH HHS U54 HG003273NHLBI Division of extramural Research HL-169458NHLBI 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 HL070825NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL169458NHLBI NIH HHS R01 HL172803NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NHLBI NIH HHS U01 HL130114NIA NIH HHS K23 AG030944NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P20 AG068024NIA NIH HHS P20 AG068053NIA NIH HHS P20 AG068077NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG038072NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 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HHS R01 AG041797NIA NIH HHS R01 AG042188NIA NIH HHS R01 AG042210NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG044829NIA NIH HHS R01 AG046949NIA NIH HHS R01 AG047649NIA NIH HHS R01 AG048234NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054047NIA NIH HHS R01 AG054073NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG057909NIA NIH HHS R01 AG058533NIA NIH HHS R01 AG059716NIA NIH HHS R01 AG060747NIA NIH HHS R01 AG061155NIA NIH HHS R01 AG063689NIA NIH HHS R01 AG064614NIA NIH HHS R01 AG064877NIA NIH HHS R01 AG069013NIA NIH HHS R01 AG070862NIA NIH HHS R01 AG079280NIA NIH HHS R37 AG015473NIA NIH HHS R56 AG051876NIA NIH HHS RC4 AG039085NIA NIH HHS RF1 AG015473NIA NIH HHS RF1 AG051504NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG054023NIA NIH HHS RF1 AG054047NIA NIH HHS RF1 AG054052NIA NIH HHS RF1 AG054074NIA NIH HHS RF1 AG054080NIA NIH HHS RF1 AG057519NIA NIH HHS RF1 AG058066NIA NIH HHS RF1 AG058267NIA NIH HHS RF1 AG058501NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA 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 AG058922NIA NIH HHS U01 AG062602NIA NIH HHS U01 AG062943NIA NIH HHS U01 AG066833NIA NIH HHS U01 AG068057NIA NIH HHS U19 AG010483NIA NIH HHS U19 AG024904NIA NIH HHS U19 AG066567NIA NIH HHS U19 AG074879NIA NIH HHS U19 AG078109NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG056270NIA NIH HHS U24 AG057437NIA NIH HHS U24 AG067418NIA NIH HHS U24 AG072122NIA NIH HHS U24 AG074855NIA NIH HHS U54 AG052427NIA NIH HHS UF1 AG047133NIBIB NIH HHS P41 EB015922NINDS 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 R01 NS080820NINDS NIH HHS U01 NS041588the National Institutes of Health R01HL169458,U01AG066833,P30AG073105Wellcome Trust
6 · The paper itself

Abstract

introductionAlzheimer's disease (AD) is a complex neurodegenerative disorder with heterogeneous genetic and molecular underpinnings. Polygenic scores (PGS) capture little of this complexity.

methodsWe conducted genome-, transcriptome-, and proteome-wide association studies (G/T/PWAS) on 15,480 individuals from the Alzheimer's Disease Sequencing Project R4 (ADSP) to identify AD-associated signals, followed by pathway enrichment analysis. Integrative risk models (IRMs) were developed using genetically regulated components of gene and protein expression and clinical covariates. Elastic-net logistic regression and random forest classifiers were evaluated using standard metrics and compared against baseline PGS.

resultsKnown and novel signals were identified via G/T/PWAS. Enrichment analyses highlighted cholesterol and immune signaling pathways. The best-performing IRM, random forest with transcriptomic and covariate features, achieved area under the receiver operating characteristic (AUROC) of 0.703 and area under the precision-recall curve (AUPRC) of 0.622, significantly outperforming PGS and baseline models. DISCUSSION: Integrating univariate discovery approaches with multivariate modeling enhances AD risk prediction and offers novel insights into underlying biological processes. HIGHLIGHTS: Identified novel contributions to Alzheimer's disease (AD) from a multi-omics perspective. Integrated genome-wide association studies (GWAS), transcriptome-wide association studies (TWAS), and proteome-wide association studies (PWAS) in a unified association study framework. Developed a method for predicting heritable risk of late-onset AD. Demonstrated that ancestry-aware modeling improves AD risk prediction accuracy.

Indexed as

Alzheimer DiseaseAgedFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMultifactorial InheritanceMultiomicsRisk AssessmentRisk FactorsTranscriptomeAlzheimer's diseaseassociation studymachine learningmulti‐omics integrationpathway enrichmentpolygenic risk scoresrisk predictionstatistical genetics

Identifiers

PMID41231230
PMCPMC12614089

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.