https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46821 CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64–4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10−5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression.]]> Wed 13 Mar 2024 15:07:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45604 Wed 02 Nov 2022 14:06:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7991 Sat 24 Mar 2018 08:35:51 AEDT ]]> https://nova.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://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39019 Fri 22 Apr 2022 09:10:54 AEST ]]>