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:42676 Wed 22 Mar 2023 14:34:07 AEDT ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:14264 −11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10⁻⁹), ANK3 (rs10994359, P = 2.5 × 10⁻⁸) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10⁻⁹).]]> Wed 11 Apr 2018 18:45:05 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:26719 -8). There were 693 and 219 independent loci with model-based replication rates ≥80% and ≥90%, respectively. Compared to analyses not incorporating relative enrichment scores, CM3 increased out-of-sample yield for SNPs that replicate at a given rate. This demonstrates that replication probabilities can be more accurately estimated using prior enrichment information with CM3.]]> Wed 11 Apr 2018 17:05:48 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:23292 Wed 11 Apr 2018 15:09:07 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:27630 Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest.]]> Wed 11 Apr 2018 14:15:34 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:28274 2(1)=7.16, p=0.007]. Conclusion: The ARCS may be sensitive to the cognitive deficits in outpatients with schizophrenia and an indicator of functional outcomes in this population.]]> Wed 11 Apr 2018 13:05:57 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34119 -4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10^-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.]]> Wed 04 Sep 2019 09:40:14 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:50043 Thu 29 Jun 2023 14:38:49 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:47202 Thu 15 Dec 2022 11:18:18 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:54811 Thu 14 Mar 2024 14:24:56 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:7405 Sat 24 Mar 2018 08:42:43 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:8286 Sat 24 Mar 2018 08:40:28 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:10315 Sat 24 Mar 2018 08:07:00 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:20081 Sat 24 Mar 2018 08:00:08 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:21465 DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.]]> Sat 24 Mar 2018 07:52:31 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:29335 Sat 24 Mar 2018 07:34:19 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:28311 Sat 24 Mar 2018 07:27:06 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:23305 Sat 24 Mar 2018 07:16:19 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:23306 Sat 24 Mar 2018 07:16:19 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:22081 Sat 24 Mar 2018 07:15:15 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:47780 Mon 30 Jan 2023 10:58:57 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:42338 N = 29,125 cases and 34,836 controls), a robust polygenic signal was observed from gene sets based on TCF4, FMR1, upregulation from MIR137 and downregulation from CHD8. Additional analyses revealed a constant floor effect in the amount of variance explained, consistent with the omnigenic model. Thus, we report that putative core gene sets showed a significant effect above and beyond the floor effect that might be linked with the underlying omnigenic background. In addition, we demonstrate a method to quantify the contribution of specific gene sets within the omnigenic context.]]> Mon 22 Aug 2022 14:00:20 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:38229 Mon 16 Aug 2021 17:39:39 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:50977 Mon 14 Aug 2023 15:24:38 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:50972 Mon 14 Aug 2023 15:19:39 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:43035 Mon 12 Sep 2022 11:49:25 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:49672 Fri 26 May 2023 15:35:47 AEST ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:46603 Fri 25 Nov 2022 16:41:41 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48644 Fri 24 Mar 2023 13:44:42 AEDT ]]>