https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34335 Wed 23 Feb 2022 16:02:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48519 p = 1.3 x 10⁻⁴) for all ischemic stroke, 0.63 (95% CI 0.50–0.80; p = 1.6 x 10⁻⁴) for cardioembolic stroke, and 0.60 (95% CI 0.44–0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67–1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88–1.21) or with any subtype. Conclusions: This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.]]> Wed 22 Mar 2023 17:11:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24807 Wed 15 Dec 2021 16:07:00 AEDT ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20390 Wed 11 Apr 2018 16:32:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18827 Wed 11 Apr 2018 13:01:16 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28417 Wed 11 Apr 2018 11:52:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20566 Wed 11 Apr 2018 10:41:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28163 Wed 11 Apr 2018 10:07:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13946 Wed 11 Apr 2018 09:27:26 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33341 Wed 09 Mar 2022 16:04:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29040 Wed 07 Jul 2021 12:14:25 AEST ]]> https://ogma.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://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19823 Tue 09 Jun 2020 09:48:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36807 Thu 04 Nov 2021 10:39:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24521 Thu 04 Nov 2021 10:38:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21442 x10^-8) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (P_IS=1.62x10^-7) and ABO (P_IS=2.6x10^-4), as well as at HDAC9 (P_LAS=2.32x10-12), 9p21 (P_LAS=3.70x10^-6), RAI1-PEMT-RASD1 (P_LAS=2.69x10^-5), EDNRA (P_LAS=7.29x10^-4), and CYP17A1-CNNM2-NT5C2 (P_LAS=4.9x10^-4). Conclusions-Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.]]> Sat 24 Mar 2018 08:05:46 AEDT ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20633 Sat 24 Mar 2018 07:55:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19418 Sat 24 Mar 2018 07:51:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20171 Sat 24 Mar 2018 07:51:43 AEDT ]]> https://ogma.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://ogma.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://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26464 Sat 24 Mar 2018 07:27:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22678 Sat 24 Mar 2018 07:12:09 AEDT ]]>