https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45194 n = 294, 95–106 years; controls: n = 1105, 55–65 years) by assessing their polygenic risk scores (PRS) based on a genome wide association study (GWAS) threshold of p < 5 x 10⁻⁵. PRS were constructed using GWAS summary data from two exceptional longevity (EL) analyses and eight cardiovascular-related risk factors (lipids) and disease (myocardial infarction, coronary artery disease, stroke) analyses. A higher genetic risk for exceptional longevity (EL) was significantly associated with longevity in our sample (odds ratio (OR) = 1.19–1.20, p = 0.00804 and 0.00758, respectively). Two cardiovascular health PRS were nominally significant with longevity (HDL cholesterol, triglycerides), with higher PRS associated with EL, but these relationships did not survive correction for multiple testing. In conclusion, ELL individuals did not have significantly lower polygenic risk for the majority of the investigated cardiovascular health traits. Future work in larger cohorts is required to further explore the role of cardiovascular-related genetic variants in EL.]]> Wed 26 Oct 2022 14:27:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34987 Wed 24 Nov 2021 15:52:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24759 -11). The results were replicated in an independent cohort, the Hunter Community Study (p < 0.002) (n = 313). Conditional and joint analysis (COJO) confirmed the association of the chromosomal 17 region with ApoH levels. The set of independent SNPs identified by COJO explained 23% of the variance. The relationships between the top SNPs and cardiovascular/lipid/cognition measures and diabetes were assessed in Sydney MAS, with suggestive results observed for diabetes and cognitive performance. However, replication of these results in the smaller OATS cohort was not found. This work provides impetus for future research to better understand the contribution of genetics to ApoH levels and its possible impacts on health.]]> Wed 15 Dec 2021 16:09:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1306 50%) compared with controls for each mutant. mIPSC decay times were unchanged in spa/spa (4.5 ± 0.3 vs 4.7 ± 0.2 ms), reduced in spd/spd (2.7 ± 0.2 vs 4.7 ± 0.2 ms), and increased in ot/ot (12.3 ± 1.2 vs 4.8 ± 0.2 ms). Thus, in spastic, GlyRs are functionally normal but reduced in number, whereas in spasmodic, GlyR kinetics is faster. The oscillator mutation results in complete absence of α1-containing GlyRs; however, some non-α1-containing GlyRs persist at synapses. Fluctuation analysis of membrane current, induced by glycine application to outside-out patches, showed that mean single-channel conductance was increased in spa/spa (64.2 ± 4.9 vs 36.1 ± 1.4 pS), but unchanged in spd/spd (32.4 ± 2.1 vs 35.3 ± 2.1 pS). GlyR-mediated whole-cell currents in spa/spa exhibited increased picrotoxin sensitivity (27 vs 71% block for 100 µM), indicating α1 homomeric GlyR expression. The picrotoxin sensitivity of evoked glycinergic IPSCs and conductance of synaptic GlyRs, as determined by nonstationary variance analysis, were identical for spa/spa and controls. Together, these findings show the three mutations disrupt GlyR-mediated inhibition via different physiological mechanisms, and the spastic mutation results in "compensatory" α1 homomeric GlyRs at extrasynaptic loci.]]> Wed 11 Apr 2018 14:28:46 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54222 Tue 13 Feb 2024 12:11:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20134 Sat 24 Mar 2018 07:51:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21021 N = 2088) and the Sydney Memory and Ageing Study (Sydney MAS, N = 541). Genotyping was undertaken using Affymetrix microarrays with imputation to HapMap2. Analyses were performed using linear regression. No genome-wide significant results were observed in HCS nor were any of the top signals replicated in Sydney MAS. Gene-based analyses in HCS identified two significant genes (ZNF295, C2CD2), but these results were not replicated in Sydney MAS. One out of eight SNPs previously associated with GS, rs550942, located near the CNTF gene, was significantly associated with GS (p = 0.005) in the HCS cohort only. Study differences may explain the lack of consistent results between the studies, including the smaller sample size of the Sydney MAS cohort. Our modest sample size also had limited power to identify variants of small effect. Our results suggest that similar to various other complex traits, many genetic variants of small effect size may influence GS. Future GWAS using larger samples and consistent measures may prove more fruitful at identifying genetic contributors for GS in middle-aged to older adults.]]> Sat 24 Mar 2018 07:50:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50640 Mon 31 Jul 2023 16:34:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33670 Mon 01 Jul 2019 09:50:58 AEST ]]>