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Jan 17, 2025;11 (3): eadr4606.

Genome-wide and phenome-wide studies provided insights into brain glymphatic system function and its clinical associations.

Lusen Ran, Yuanyuan Fang, Chang Cheng, Yuqin He, Zhonghe Shao, Yifan Kong, Hao Huang, Shabei Xu, Xiang Luo, Wei Wang, Xingjie Hao, Minghuan Wang
Author Information
  1. Lusen Ran: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  2. Yuanyuan Fang: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  3. Chang Cheng: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  4. Yuqin He: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  5. Zhonghe Shao: Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  6. Yifan Kong: Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  7. Hao Huang: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  8. Shabei Xu: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  9. Xiang Luo: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  10. Wei Wang: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  11. Xingjie Hao: Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
  12. Minghuan Wang: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ORCID
PMID: 39823331 DOI: 10.1126/sciadv.adr4606

Abstract

We applied an MRI technique diffusion tensor imaging along the perivascular space (DTI-ALPS) for assessing glymphatic system (GS) in a genome-wide association study (GWAS) and phenome-wide association study (PheWAS) of 40,486 European individuals. Exploratory analysis revealed 17 genetic loci significantly associating with the regional DTI-ALPS index. We found 58 genes, including and , which prioritized in the DTI-ALPS index subtypes and associated with neurodegenerative diseases. PheWAS of 241 traits suggested that body mass index and blood pressure phenotypes closely related to GS function. Moreover, we detected disrupted GS function in 44 of 625 predefined disease conditions. Notably, Mendelian randomization and mediation analysis indicated that lower DTI-ALPS index was a risk factor for ischemic stroke (odds ratio = 1.56, = 0.028) by partly mediating the risk factor of obesity. Results provide insights into the genetic architecture and mechanism for the DIT-ALPS index and highlight its great clinical value, especially in cerebral stroke.

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MeSH Term

Humans
Genome-Wide Association Study
Glymphatic System
Phenotype
Brain
Diffusion Tensor Imaging
Genetic Predisposition to Disease
Phenomics
Male
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
Female
Journal Article
Article has an altmetric score of 10

Word Cloud

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