https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.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://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34724 Thu 17 Feb 2022 09:27:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36726 ɛ4/ɛ3> ɛ3/ɛ3> ɛ2/ɛ3> ɛ2/ɛ2). The greatest variation in lipids was related to the ɛ2 isoform, where various lysophosphatidylcholines and all phosphatidylethanolamine (PE) subclasses were elevated relative to ɛ3/ɛ3 and ɛ4 carriers. APOE ɛ4 carriers had reduced phosphatidylinositol relative to ɛ3/ɛ3 and ɛ2 carriers. Logistic regression revealed that ɛ2 carriers were at least 4 times higher odds of being in the highest tertile of PE lipid level relative to ɛ3/ɛ3. The elevation in PE and other phospholipids in ɛ2 carriers may indicate the protective effect of ɛ2 is linked to these phospholipids. Additionally, high baseline PE in cognitively normal participants predicted protection against cognitive decline six years later. Our data suggest substantial modulation of plasma lipids by APOE genotype and therefore indicates possible lipid targets and pathomechanisms involved in AD risk.]]> Thu 02 Jul 2020 09:10:42 AEST ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33670 Mon 01 Jul 2019 09:50:58 AEST ]]>