https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16959 -7), with independent replication in a second population (p = 0.0048, OR(95% CI) = 1.18(1.05–1.32); meta-analysis p = 2.6×10^-8). The nearby gene, MMP12, was significantly over expressed in carotid plaques compared to atherosclerosis-free control arteries (p = 1.2×10^-15; fold change = 335.6). Permutation analyses demonstrated improved significance for associations when accounting for age-at-onset in all four stroke phenotypes (p<0.001). Our results show that a covariate-informed design, by adjusting for age-at-onset of stroke, can detect variants not identified by conventional GWAS.]]> Wed 11 Apr 2018 17:21:31 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20390 Wed 11 Apr 2018 16:32:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18827 Wed 11 Apr 2018 13:01:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28417 Wed 11 Apr 2018 11:52:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13946 Wed 11 Apr 2018 09:27:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27769 SNP]) and tested the hypothesis that WMH heritability differs between hypertensive and nonhypertensive individuals. Methods: WMHV was measured on MRI in the stroke-free cerebral hemisphere of 2336 ischemic stroke cases with GWAS data. After adjustment for age and intracranial volume, we determined which cardiovascular risk factors were independent predictors of WMHV. Using the genome-wide complex trait analysis tool to estimate H_SNP for WMHV overall and within subgroups stratified by risk factors found to be significant in multivariate analyses. Results: A significant proportion of the variance of WMHV was attributable to common SNPs after adjustment for significant risk factors (H_SNP=0.23; P=0.0026). H_SNP estimates were higher among hypertensive individuals (H_SNP=0.45; P=7.99x10^-5); this increase was greater than expected by chance (P=0.012). In contrast, estimates were lower, and nonsignificant, in nonhypertensive individuals (H_SNP=0.13; P=0.13). Conclusions: A quarter of variance is attributable to common SNPs, but this estimate was greater in hypertensive individuals. These findings suggest that the genetic architecture of WMH in ischemic stroke differs between hypertensives and nonhypertensives. Future WMHV GWAS studies may gain power by accounting for this interaction.]]> Tue 21 Jul 2020 09:44:12 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28335 0.01 were included in the analysis. A significance level of P<0.0015 was used, adjusted for the effective number of independent SNPs in the region using the Galwey method. Results: We found no association of any common variants in NOTCH3 (including rs10404382, rs1043994, rs10423702, and rs1043997) with lacunar stroke or white matter hyperintensity volume. We repeated our analysis stratified for hypertension but again found no association. Conclusions: Our study does not support a role for common NOTCH3 variation in the risk of sporadic small-vessel disease.]]> Tue 21 Jul 2020 09:43:47 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19823 Tue 09 Jun 2020 09:48:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51452 2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. Results: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location–specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location. Discussion: Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.]]> Tue 05 Sep 2023 18:01:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24521 Thu 04 Nov 2021 10:38:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19050 2-fold increased risk of IS compared with subjects in the lowest quintile. Addition of the combined GRS to a simple model based on sex significantly improved the prediction of IS in the combined clinic-based samples but not in the population-based studies, and there was no significant improvement in net reclassification. Conclusions - A multilocus GRS based on common variants for established cardiovascular risk factors was significantly associated with IS both in clinic-based samples and in the general population. However, the improvement in clinical risk prediction was found to be small.]]> Sat 24 Mar 2018 08:05:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20633 Sat 24 Mar 2018 07:55:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25277 −11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28–1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.]]> Sat 24 Mar 2018 07:38:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30052 -8; joint OR 1·19, 1·12-1·26, p=1·30 × 10^-9). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26 × 10^-19; joint OR 1·37, 1·30-1·45, p=2·79 × 10^-32) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93 × 10^-7; joint OR 1·17, 1·11-1·23, p=2·29 × 10^-10) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50 × 10^-8; joint OR 1·24, 1·15-1·33, p=4·52 × 10^-9) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82 × 10^-8; joint OR 1·17, 1·11-1·23, p=2·92 × 10^-9). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed. Interpretation: Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility.]]> Sat 24 Mar 2018 07:31:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25600 -28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p 2.7 x 10^-20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.]]> Sat 24 Mar 2018 07:28:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25211 Sat 24 Mar 2018 07:14:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39002 3 ) was associated with age (β −0.3 [per 14.4 years]), male sex (β 1.0), and prior stroke (β −0.2). In the multivariable outcome model, brain volume was an independent predictor of modified Rankin Scale score (β −0.233), with reduced odds of worse long-term functional outcomes (odds ratio, 0.8; 95% CI, 0.7-0.9) in those with larger brain volumes. Conclusion: Larger brain volume quantified on clinical magnetic resonance imaging of patients with AIS at the time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of the mechanisms of poststroke recovery.]]> Mon 29 Jan 2024 17:46:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48737 Fri 31 Mar 2023 16:23:23 AEDT ]]>