Analysis of genetic variability and whole genome linkage of whole-brain, subcortical, and ependymal hyperintense white matter volume
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Background and Purpose— The cerebral volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity. Pathophysiology studies identified that subcortical and ependymal HWM are produced by 2 different mechanisms but shared a common risk factor: high arterial pulse pressure. Recent studies have demonstrated high heritability of the whole-brain HMW volume and reported significant and suggestive evidence of genetic linkage. We performed heritability and whole-genome linkage analysis to replicate previous reported findings and to study shared genetic variance, and possible overlap for specific loci, between subcortical and ependymal HWM volumes in a population of healthy Mexican Americans. Methods— The volumes of subcortical and ependymal HWM regions were measured from high-resolution (1 mm 3 ), 3-dimensional fluid-attenuated inversion recovery images acquired for 459 (283 females, 176 males) active participants in the San Antonio Family Heart Study. Subjects ranged in age from 19 to 85 years of age (47.9±13.5 years) and were part of 49 families (9.4±8.5 individuals per family). Results— The volumes of whole-brain, subcortical, and ependymal HWM were highly heritable ( h 2 =0.72, 0.66, and 0.73, respectively). The subcortical and ependymal HWM volumes shared 21% of genetic variability indicating significant pleiotropy. Genomewide linkage analysis showed only a suggestive bivariate linkage for subcortical and ependymal HWM volumes (log of odds=2.12) on chromosome 1 at 288 cM. Conclusion— We replicated previous findings of high heritability for the whole-brain HWM volume. We also showed that subcortical and ependymal volume shared a significant portion of genetic variability and the bivarate linkage analysis produced a suggestive linkage near the locus previously identified in a study of whole-brain HWM volume and arterial pulse pressure.
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The association between SVD and blood pressure may be at the genetic locus level rather than directly causal.
“It is possible that the association between SVD and BP is at the genetic locus level rather than being directly causal.94,95”
From Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging (2013) · cites this paper as [94]
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Beecham, A. H., Dong, C., Wright, C. B., Dueker, N., Brickman, A. M., Wang, L., DeCarli, C. S., Blanton, S. H., Rundek, T., Mayeux, R. P., et al. (2017) · Neurology Genetics · doi:10.1212/nxg.0000000000000185 · Cited by 13 · see citing works
3DCNN predicting brain age using diffusion tensor imaging
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Dissecting Polygenic Etiology of Ischemic Stroke in the Era of Precision Medicine
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Unravelling the genetic architecture of cerebral small vessel disease in the context of stroke
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Conceptualizing Major Depression
Glahn, D. C., Knowles, E. E. M., Mathias, S. R., Almasy, L. A., Hodgson, K., Yao, N., Olvera, R. L., Curran, J. E., & Blangero, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800105-9.00031-7 · Cited by 1 · see citing works
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Progression of White Matter Hyperintensities in older adults: A systematic review and meta-analysis
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- Authors
- Kochunov, P., Glahn, D., Winkler, A., Duggirala, R., Olvera, R. L., Cole, S., Dyer, T. D., Almasy, L., Fox, P. T., & Blangero, J.
- Affiliations
- Texas Biomedical Research Institute (US)
- ORCID
- Venue
- Stroke
- Published
- 2009-12
- Volume
- 40
- Issue
- 12
- Pages
- 3685-3690
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- PMC
- PMC2787844
- OpenAlex
- W2161730586
- Cited by
- 54
- References
- 43
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2020: 1 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 3 · 2013: 5 · 2012: 5
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ORBi (University of Liège) (submittedVersion, other-oa)
- ScholarWorks @ UTRGV (The University of Texas Rio Grande Valley) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH078111, R01S MH078111, MH0708143, -MH078111, RO1s MH078111, R01MH083824, MH083824)
- National Institute of Biomedical Imaging and Bioengineering (K01EB006395)
- Topics
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- white matter hyperintensities, heritability, genetic linkage, subcortical white matter, pleiotropy, pulse pressure, San Antonio Family Heart Study, Mexican Americans
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Brain Ischemia, Chromosome Mapping, DNA Mutational Analysis, Ependyma, Female, Genetic Testing, Humans, Genetic Linkage, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Fibers, Myelinated, Genetic Variation, Cerebrospinal Fluid Pressure, Cohort Studies, Biomarkers, Mexican Americans, Disease Progression, Intracranial Hypertension, Genetic Predisposition to Disease, Cerebrum, Young Adult, Leukoencephalopathies
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