ArticleBMC medical genomics2009
Complexity in the genetic architecture of leukoaraiosis in hypertensive sibships from the GENOA Study.
Article in BMC medical genomics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Neighborhood environment associations with cognitive function and structural brain measures in older African Americans.BMC medicine · 2025Article
- Leukoaraiosis: Epidemiology, Imaging, Risk Factors, and Management of Age-Related Cerebral White Matter Hyperintensities.Journal of stroke · 2024Review
- Human Genetic Variation in F3 and Its Impact on Tissue Factor-Dependent Disease.Seminars in thrombosis and hemostasis · 2024Review
- Epigenome-wide association study identifies DNA methylation sites associated with target organ damage in older African Americans.Epigenetics · 2021Article
- Transportation Physical Activity Earlier in Life and Areas of the Brain related to Dementia Later in Life.Journal of transport & health · 2021Article
- Article
- Intrinsic and extrinsic epigenetic age acceleration are associated with hypertensive target organ damage in older African Americans.BMC medical genomics · 2019Article
- A comparison of manual tracing and FreeSurfer for estimating hippocampal volume over the adult lifespan.Human brain mapping · 2018Article
- DNA Methylation Profiling Reveals the Change of Inflammation-AssociatedFrontiers in aging neuroscience · 2018Article
- Association between Low-density lipoprotein cholesterol and occipital periventricular hyperintensities in a group of Chinese patients: an observational study.Lipids in health and disease · 2017Observational
- Multiple Factors Involved in the Pathogenesis of White Matter Lesions.BioMed research international · 2017Review
- Analysis of genetic polymorphisms associated with leukoaraiosis in the southern Chinese population: A case-control study.Medicine · 2016Article
- Epigenomic Indicators of Age in African Americans.Hereditary genetics : current research · 2014Article
- C-reactive protein and cognition are unrelated to leukoaraiosis.TheScientificWorldJournal · 2014Article
- Gene-specific DNA methylation association with serum levels of C-reactive protein in African Americans.PloS one · 2013Article
- NINJ2 SNP may affect the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions.BMC research notes · 2012Article
- Aortic pulse wave velocity is associated with measures of subclinical target organ damage.JACC. Cardiovascular imaging · 2011Article
- Identification of epistatic effects using a protein-protein interaction database.Human molecular genetics · 2010Article
- SNP-SNP interactions dominate the genetic architecture of candidate genes associated with left ventricular mass in African-Americans of the GENOA study.BMC medical genetics · 2010Article
- Hyperlipidemia and reduced white matter hyperintensity volume in patients with ischemic stroke.Stroke · 2010Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundSubcortical white matter hyperintensity on magnetic resonance imaging (MRI) of the brain, referred to as leukoaraiosis, is associated with increased risk of stroke and dementia. Hypertension may contribute to leukoaraiosis by accelerating the process of arteriosclerosis involving penetrating small arteries and arterioles in the brain. Leukoaraiosis volume is highly heritable but shows significant inter-individual variability that is not predicted well by any clinical covariates (except for age) or by single SNPs.
methodsAs part of the Genetics of Microangiopathic Brain Injury (GMBI) Study, 777 individuals (74% hypertensive) underwent brain MRI and were genotyped for 1649 SNPs from genes known or hypothesized to be involved in arteriosclerosis and related pathways. We examined SNP main effects, epistatic (gene-gene) interactions, and context-dependent (gene-environment) interactions between these SNPs and covariates (including conventional and novel risk factors for arteriosclerosis) for association with leukoaraiosis volume. Three methods were used to reduce the chance of false positive associations: 1) false discovery rate (FDR) adjustment for multiple testing, 2) an internal replication design, and 3) a ten-iteration four-fold cross-validation scheme.
resultsFour SNP main effects (in F3, KITLG, CAPN10, and MMP2), 12 SNP-covariate interactions (including interactions between KITLG and homocysteine, and between TGFB3 and both physical activity and C-reactive protein), and 173 SNP-SNP interactions were significant, replicated, and cross-validated. While a model containing the top single SNPs with main effects predicted only 3.72% of variation in leukoaraiosis in independent test samples, a multiple variable model that included the four most highly predictive SNP-SNP and SNP-covariate interactions predicted 11.83%.
conclusionThese results indicate that the genetic architecture of leukoaraiosis is complex, yet predictive, when the contributions of SNP main effects are considered in combination with effects of SNP interactions with other genes and covariates.
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Registered trials
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.