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: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:15141 Wed 11 Apr 2018 13:54:12 AEST ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:17347 Sat 24 Mar 2018 08:01:42 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:20633 Sat 24 Mar 2018 07:55:46 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:20171 Sat 24 Mar 2018 07:51:43 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: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://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:30005 Mon 17 Oct 2022 12:06:14 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:42483 p = 1.1 x 10⁻⁸). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96−1.30, p = 0.14; p for heterogeneity = 2.6 x 10⁻³) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84−1.33, p = 0.64; p for heterogeneity = 8.6 x 10⁻³) when compared with that for CHD. Conclusions: In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.]]> Fri 26 Aug 2022 13:56:54 AEST ]]>