https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.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://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: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: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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41379 Tue 04 Apr 2023 19:08:51 AEST ]]> 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: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:27385 -6) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. Results: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 x 10^-10) and replication cohorts (p = 5.65 x 10^-8). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 x 10^-8, and rs6813517 [SPOCK3], p = 2.58 x 10^-8) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. Conclusions: This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.]]> Sat 24 Mar 2018 07:34:11 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: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: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:47296 Fri 13 Jan 2023 10:45:52 AEDT ]]>