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| 15. |
- Franceschini, N, et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
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Tidskriftsartikel (refereegranskat)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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| 18. |
- Jia, TY, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:8, s. 3884-3895
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
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| 20. |
- Kharitonova, T, et al.
(författare)
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Hyperdense middle cerebral artery sign on admission CT scan--prognostic significance for ischaemic stroke patients treated with intravenous thrombolysis in the safe implementation of thrombolysis in Stroke International Stroke Thrombolysis Register
- 2009
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Ingår i: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 27:1, s. 51-59
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Hyperdense middle cerebral artery sign (HMCAS) on CT scan before stroke thrombolysis is associated with increased risk for haemorrhage and unfavourable outcome in several small studies. <i>Methods:</i> We examined baseline characteristics, intracranial haemorrhage and outcomes of intravenous thrombolysis in patients with and without HMCAS using the internet-based Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. Symptomatic intracerebral haemorrhage (SICH) was defined as a National Institute of Health Stroke Scale (NIHSS) score decrease of ≥4 points plus type 2 parenchymal haemorrhage on imaging [Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST) definition], or any haemorrhage on follow-up imaging combined with a decrease of at least 1 point on the NIHSS [randomized controlled trial (RCT) definition]. Three-month outcomes were mortality and independence (modified Rankin scale score = 0–2). <i>Results:</i> 1,905 of 10,023 (19.0%) patients had HMCAS. Patients with HMCAS (vs. no HMCAS) were younger (median age 68 vs. 70 years, p < 0.001), had severer stroke (baseline NIHSS score 17 vs. 11, p < 0.05), higher mortality [23% (95% CI 20.0–25.1) vs. 13% (95% CI 12.1–13.7)] and lower independence [31% (95% CI 28.5–33.0) vs. 56% (95% CI 54.8–57.2)]. SICH rates per the SITS-MOST were 1.3% (95% CI 0.8–1.9) versus 1.8% (95% CI 1.5–2.1) and per the RCT definition 10.3% (95% CI 9.0–11.8) versus 6.8% (95% CI 6.2–7.3). In multivariable analysis, HMCAS was not an independent predictor of SICH but of mortality and independence per the SITS-MOST. <i>Conclusions:</i> HMCAS patients had severer stroke and a worse 3-month outcome. The risk for SICH per the SITS-MOST definition was similar compared to non-HMCAS patients, although increased per the RCT definition. There is not sufficient evidence to exclude these patients from intravenous thrombolysis. Combined treatment approaches might be considered in the perspective of the severe outcome and evaluated in RCTs.
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