https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34568 Wed 17 Nov 2021 16:28:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24491 -6) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p 2.2 x 10^-8; rs941898 [EVL], p 4.0 x 10^-8; rs962888 [C1QL1], p 1.1 x 10^-8; rs9515201 [COL4A2], p 6.9 x 10^-9). Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.]]> Wed 15 Dec 2021 16:08:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36509 Wed 15 Dec 2021 16:07:52 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:13946 Wed 11 Apr 2018 09:27:26 AEST ]]> 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:47666 Tue 24 Jan 2023 15:47:40 AEDT ]]> 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:27705 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes. Conclusions: Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry.]]> Tue 21 Jul 2020 09:43:56 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:24521 Thu 04 Nov 2021 10:38:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13951 Sat 24 Mar 2018 10:41:26 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: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:27245 g=0.96, SE=0.47, P=9x10⁻⁴) and profile scores (r_g=0.72; 95% confidence interval, 0.52–0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1x10⁻⁷) for single nucleotide polymorphisms near the opioid receptor μ1 (OPRM1) gene. Conclusions: Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes.]]> Sat 24 Mar 2018 07:29:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25883 Sat 24 Mar 2018 07:25:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28358 –8) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 x 10^–186), rs10665 with FVII (p = 2.4 x 10^–47), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 x 10^–57) and factor VIII (p = 1.2 x 10^–36). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88–0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). Interpretation: ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype. Ann Neurol 2013]]> Sat 24 Mar 2018 07:25:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22678 Sat 24 Mar 2018 07:12:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48737 Fri 31 Mar 2023 16:23:23 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42223 P=0.0007; odds ratio=0.89; 95% CI, 0.82–0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91–0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80–0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89–0.98) whereas imbalance without ohnologs lacked such an association. Conclusions: Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.]]> Fri 26 Aug 2022 09:34:08 AEST ]]>