https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 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: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:41899 PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.]]> Tue 16 Aug 2022 08:27:58 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9346 Sat 24 Mar 2018 08:36:28 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18169 Sat 24 Mar 2018 08:04:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20368 Sat 24 Mar 2018 07:58:11 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:4620 Sat 24 Mar 2018 07:21:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4619 Sat 24 Mar 2018 07:21:53 AEDT ]]>