| Title: | Genome-wide and phenome-wide studies provided insights into brain glymphatic system function and its clinical associations |
| Journal: | Science Advances |
| Published: | 17 Jan 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39823331/ |
| DOI: | https://doi.org/10.1126/sciadv.adr4606 |
Publication 14500
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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 SPPL2C and EFCAB5, 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, P = 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.</p>
12 Keywords
- Brain
- Diffusion Tensor Imaging
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Glymphatic System
- Humans
- Male
- Mendelian Randomization Analysis
- Phenomics
- Phenotype
- Polymorphism, Single Nucleotide
12 Authors
- Lusen Ran
- Yuanyuan Fang
- Chang Cheng
- Yuqin He
- Zhonghe Shao
- Yifan Kong
- Hao Huang
- Shabei Xu
- Xiang Luo
- Wei Wang
- Xingjie Hao
- Minghuan Wang
1 Application
| Application ID | Title |
|---|---|
| 90311 | Association of Lifestyle Behaviors and Genetic Risk With cardio-cerebrovascular diseases. |
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