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:15141 Wed 11 Apr 2018 13:54:12 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:30590 Tue 20 Aug 2024 12:05:56 AEST ]]> 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: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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:28431 140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.]]> Sat 24 Mar 2018 07:29:03 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:23785 5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.]]> Sat 24 Mar 2018 07:16:26 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:22322 FBXL20 (P = 5.6 × 10⁻⁹) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10⁻⁴–2.2 × 10⁻⁷. Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.]]> Sat 24 Mar 2018 07:14:43 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:47296 Fri 13 Jan 2023 10:45:52 AEDT ]]>