Evidence map›Paper›PMID 39837893›Full record

ArticleNPJ Parkinson's disease2025

A network-based systems genetics framework identifies pathobiology and drug repurposing in Parkinson's disease.

Lijun Dou, Zhenxing Xu, Jielin Xu, Chengxi Zang, Chang Su, Andrew A Pieper, James B Leverenz, Fei Wang, Xiongwei Zhu, Jeffrey Cummings and 1 more

Abstract read
In one paragraph

Article in NPJ Parkinson's disease, 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. Article
  2. Article
  3. Target discovery and drug design in the era of artificial intelligence.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  4. Network-based prediction and real-world patient data observation identify doxycycline as a repurposable drug in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  5. Review
  6. Review
  7. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Lijun DouCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Zhenxing XuDepartment of Population Health Sciences, Weill Cornell Medical College, Cornell University, New York, NY, 10065, USA.
Jielin XuCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Chengxi ZangDepartment of Population Health Sciences, Weill Cornell Medical College, Cornell University, New York, NY, 10065, USA.
Chang SuDepartment of Population Health Sciences, Weill Cornell Medical College, Cornell University, New York, NY, 10065, USA.
Andrew A PieperDepartment of Psychiatry, Case Western Reserve University, Cleveland, OH, USA.
James B LeverenzDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.
Fei WangDepartment of Population Health Sciences, Weill Cornell Medical College, Cornell University, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-9459-9461
Xiongwei ZhuDepartment of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA.
Jeffrey CummingsChambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, Kirk Kerkorian School of Medicine, UNLV, Las Vegas, NV, 89154, USA.
Feixiong ChengCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. chengf@ccf.org.ORCID http://orcid.org/0000-0002-1736-2847

Funding

Translational and Therapeutics CoreP30AG072959 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI JAGAN AYYAPPAN PILLAI · 2021 to 2026
$23.9M
Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8M
Endophenotype Network-based Approaches to Prediction and Population-based Validation of In Silico Drug Repurposing for Alzheimer's DiseaseR01AG066707 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng · 2020 to 2026
$4.9M
TREM2 Genotype-Informed Drug Repurposing and Combination Therapy Design for Alzheimer’s DiseaseR01AG076448 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng, Li Gan · 2022 to 2026
$4.0M
Alzheimer's MultiOme Data Repurposing: Artificial Intelligence, Network Medicine, and Therapeutics DiscoveryU01AG073323 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BEKRIS, LYNN, CHENG, FEIXIONG · 2021 to 2025
$4.0M
Alzheimer's Clinical Trial InnOvatioN (ACTION) InitiativeR35AG071476 · NIA · UNIVERSITY OF NEVADA LAS VEGAS · PI CUMMINGS, JEFFREY L. · 2021 to 2025
$2.9M
Alzheimer's Disease and Related Dementia-like Sequelae of SARS-CoV-2 Infection: Virus-Host Interactome, Neuropathobiology, and Drug RepurposingRF1AG082211 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI CHENG, FEIXIONG, PIEPER, ANDREW A · 2023 to 2023
$2.4M
Characterize neuronal and glial cell-specific vulnerability to proteinopathies in Alzheimer's disease using multimodal single-nuclei genomic and epigenomic approachesR01AG082118 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BONAKDARPOUR, BORNA, CHENG, FEIXIONG · 2023 to 2025
$2.4M
Dark GPCR signaling underlying the Microbiome-Gut-Brain Axis for Alzheimer's Disease and Related DementiaRF1NS133812 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BROWN, JONATHAN MARK, CHENG, FEIXIONG · 2023 to 2023
$2.3M
Microglial Activation and Inflammatory Endophenotypes Underlying Sex Differences of Alzheimer’s DiseaseR01AG084250 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng, Justin D. Lathia · 2023 to 2026
$2.2M
Multimodal single-cell genomic and epigenomic analyses elucidate Alzheimer’s sexual dimorphism in human immune systems agingR56AG074001 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BEKRIS, LYNN, CHENG, FEIXIONG · 2021 to 2021
$1.2M
Alzheimer's Disease and Related Dementias Innovation Incubator (InnovaTor)R25AG083721 · NIA · UNIVERSITY OF NEVADA LAS VEGAS · PI JEFFREY L. CUMMINGS, Xue K Zhong · 2023 to 2026
$1.0M
NIA NIH HHS P30 AG072959NIA NIH HHS R01 AG066707NIA NIH HHS R01 AG076448NIA NIH HHS R01 AG082118NIA NIH HHS R01 AG084250NIA NIH HHS R21 AG083003NIA NIH HHS R25 AG083721NIA NIH HHS R35 AG071476NIA NIH HHS R56 AG074001NIA NIH HHS RF1 AG082211NIA NIH HHS U01 AG073323NIGMS NIH HHS P20 GM109025NINDS NIH HHS RF1 NS133812U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG066707U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG076448U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG084250U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01AG073323
6 · The paper itself

Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments only manage symptoms and lack the ability to slow or prevent disease progression. We utilized a systems genetics approach to identify potential risk genes and repurposable drugs for PD. First, we leveraged non-coding genome-wide association studies (GWAS) loci effects on five types of brain-specific quantitative trait loci (xQTLs, including expression, protein, splicing, methylation and histone acetylation) under the protein-protein interactome (PPI) network. We then prioritized 175 PD likely risk genes (pdRGs), such as SNCA, CTSB, LRRK2, DGKQ, and CD44, which are enriched in druggable targets and differentially expressed genes across multiple human brain-specific cell types. Integrating network proximity-based drug repurposing and patient electronic health record (EHR) data observations, we identified Simvastatin as being significantly associated with reduced incidence of PD (hazard ratio (HR) = 0.91 for fall outcome, 95% confidence interval (CI): 0.87-0.94; HR = 0.88 for dementia outcome, 95% CI: 0.86-0.89) after adjusting for 267 covariates. In summary, our network-based systems genetics framework identifies potential risk genes and repurposable drugs for PD and other neurodegenerative diseases if broadly applied.

Identifiers

PMID39837893
PMCPMC11751448

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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.