| Title: | Genetic Susceptibility to Cardio-Cerebrovascular Diseases and White Matter Integrity in Asymptomatic Older Adults: A UK Biobank Observational Cohort Study |
| Journal: | Journal of Magnetic Resonance Imaging |
| Published: | 12 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40650550/ |
| DOI: | https://doi.org/10.1002/jmri.70042 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmri.70042 |
Publication 16977
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: Cardio-cerebrovascular diseases are linked to neuroanatomical changes that may arise from genetic risk profiles, with structural brain alterations often preceding clinical onset. The pathways connecting genetic susceptibility to early neuroimaging phenotypes remain unclear.</p>
PURPOSE: To examine the effects of polygenic risk for cardio-cerebrovascular diseases (PRSCCVD) on brain structure in healthy middle-aged and older adults.</p>
STUDY TYPE: Observational cohort study.</p>
POPULATION: 29,714 healthy White British individuals (mean age 54.86 ± 7.44 years; 13,691 male).</p>
FIELD STRENGTH/SEQUENCE: 3T MRI; 3D-MPRAGE T1, DTI (monopolar Stejskal-Tanner).</p>
ASSESSMENT: Brain structural measurements were derived from 48 white matter tracts (Johns Hopkins University atlas) using eight diffusion MRI metrics for white matter microstructure, and from 62 cortical regions (Desikan-Killiany-Tourville atlas) for cortical thickness and surface area measurements. Confirmatory factor analysis was applied to calculate the polygenic risk score for PRSCCVD based on PRS scores for cardiovascular disease, coronary artery disease, and ischemic stroke.</p>
STATISTICAL TESTS: Associations between PRSCCVD and 508 brain structural MRI phenotypes were examined using multivariate linear regression with Bonferroni correction. Comparative analyses between gray and white matter phenotypes, as well as between older (≥ 60 years) and middle-aged (< 60 years) participants, were performed using Wilcoxon signed-rank tests (p < 0.05). Propensity score matching was applied to balance covariates in age-related effect analyses.</p>
RESULTS: PRSCCVD was significantly associated with 117 white matter (β range: -0.042 to 0.051, partial R 2 range: 0.29% to 0.05%) and two cortical phenotypes (bilateral insular: β = -0.023, partial R 2 range: 0.05%-0.06%) in healthy middle-aged and older adults. White matter microstructure was more vulnerable than cortical morphometry (W = 37,912). Older adults had more severe white matter microstructure damage than the middle-aged people (W = 49,046).</p>
DATA CONCLUSION: PRSCCVD preferentially affects white matter microstructure over cortical morphometry in asymptomatic individuals, with exacerbated effects in older adults.</p>
EVIDENCE LEVEL: 3.</p>
TECHNICAL EFFICACY: 2.</p>
17 Keywords
- Aged
- Biological Specimen Banks
- Brain
- Cardiovascular Diseases
- Cerebrovascular Disorders
- Cohort Studies
- Diffusion Tensor Imaging
- Female
- Genetic Predisposition to Disease
- Humans
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Risk Factors
- UK Biobank
- United Kingdom
- White Matter
5 Authors
- Jingchun Liu
- Caihong Wang
- Yujie Zhang
- Wen Qin
- Chunshui Yu
1 Application
| Application ID | Title |
|---|---|
| 75556 | Trans-ethnic genome-wide and exposome-wide association studies of neuroimaging and behavioral phenotypes |
Enabling scientific discoveries that improve human health