https://novaprd-lb.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:33544 -9). The lead single-nucleotide polymorphism (rs12445022) was also associated with cerebral white matter hyperintensities (OR [95% CI] = 1.10 [1.05-1.16] ; p = 5.3 × 10^-5 ; N = 3,670), but not intracerebral hemorrhage (OR [95% CI] = 0.97 [0.84-1.12] ; p = 0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p = 9.4 × 10^-7) and DNA methylation at probe cg16596957 in whole blood (p = 5.3 × 10^-6). Interpretation: 16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements.]]> Wed 15 Dec 2021 16:10:00 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:24389 -6 and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. Results: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5x10^-9). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII.activating protease levels, a product of HABP2. Conclusions: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.]]> Wed 15 Dec 2021 16:09:44 AEDT ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:24807 Wed 15 Dec 2021 16:07:00 AEDT ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:20390 Wed 11 Apr 2018 16:32:40 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:18827 Wed 11 Apr 2018 13:01:16 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:28417 Wed 11 Apr 2018 11:52:24 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:38111 [BI] = 9.38 × 10^-25; p_[SSBI] = 5.23 × 10-14 for hypertension), smoking (p_[BI]= 4.4 × 10^-10; p_[SSBI] = 1.2 × 10^-4), diabetes (p_[BI] = 1.7 × 10 -8; p_[SSBI] = 2.8 × 10^-3), previous cardiovascular disease (p_[BI] = 1.0 × 10^-18; p_[SSBI] = 2.3 × 10^-7), stroke (p_[BI] = 3.9 × 10^-69; p_[SSBI] = 3.2 × 10^-24), and MRI-defined white matter hyperintensity burden (p_[BI]=1.43 × 10^-157; p_[SSBI] = 3.16 × 10^-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p = 0.0022), without indication of directional pleiotropy. Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.]]> Wed 04 Aug 2021 10:54:18 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:47666 Tue 24 Jan 2023 15:47:40 AEDT ]]> https://novaprd-lb.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://novaprd-lb.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://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:24521 Thu 04 Nov 2021 10:38:38 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:19418 Sat 24 Mar 2018 07:51:57 AEDT ]]> https://novaprd-lb.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://novaprd-lb.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://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:25883 Sat 24 Mar 2018 07:25:54 AEDT ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:22678 Sat 24 Mar 2018 07:12:09 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48737 Fri 31 Mar 2023 16:23:23 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:13946 Fri 30 Aug 2024 14:11:56 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:55383 Fri 24 May 2024 10:35:40 AEST ]]>