https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42701 Wed 22 Mar 2023 15:07:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25928 −9) more prevalent in genomic regions that are likely to have undergone recent positive selection in humans (i.e., with a low NSS score). Variants in brain-related genes with a low NSS score confer significantly higher susceptibility than variants in other brain-related genes. The enrichment is strongest for schizophrenia, but we cannot rule out enrichment for other phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development. Conclusions: Our results suggest that there is a polygenic overlap between schizophrenia and NSS score, a marker of human evolution, which is in line with the hypothesis that the persistence of schizophrenia is related to the evolutionary process of becoming human.]]> Wed 12 Aug 2020 09:42:59 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34209 Wed 09 Feb 2022 15:53:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55164 Thu 18 Apr 2024 10:52:05 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34615 Thu 04 Apr 2019 09:04:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21752 Sat 24 Mar 2018 08:03:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17373 Sat 24 Mar 2018 08:01:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20171 Sat 24 Mar 2018 07:51:43 AEDT ]]> 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:29641 Sat 24 Mar 2018 07:41:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26041 Sat 24 Mar 2018 07:26:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42186 n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.]]> Fri 26 Aug 2022 10:49:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46603 Fri 25 Nov 2022 16:41:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47250 Fri 16 Dec 2022 12:29:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44100 –9 and replicated the finding in the validation set (OR 1.48; 95% CI 1.09–1.99; P = .01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32–1.98; P = 4.0 × 10^–6; allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21–1.56; P = 1.5 × 10^–6; allele frequency = 11.5%). Among amoxicillin- and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A*02:01 and DRB1*15:01. Conclusions: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.]]> Fri 07 Oct 2022 14:21:42 AEDT ]]>