https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Classification of schizophrenia using differential gene expression in peripheral blood lymphocytes https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:2967 Wed 24 Jul 2013 22:50:59 AEST ]]> Novel blood pressure locus and gene discovery using genome-wide association study and expression data sets from blood and the kidney https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34209 Wed 20 Feb 2019 10:21:56 AEDT ]]> Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37129 via the integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large-scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse-variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin-like growth factor receptor 1 and other membrane receptors (OR: 0.82-1.18, p values: 6.96 × 10-43.28 × 10-8), are linked to insulin resistance and estrogen receptor signaling pathways. Proteins identified at other loci include those involved in biological processes such as alcohol and lipid metabolism, proteolysis, apoptosis, immune regulation and cell motility and proliferation. Consistent associations were observed for 22 proteins in the UK Biobank data (p < 0.05). The study identifies potential novel biomarkers for breast cancer, but further investigation is needed to replicate our findings.]]> Wed 19 Aug 2020 12:59:44 AEST ]]> Leveraging genomic annotations and pleiotropic enrichment for improved replication rates in schizophrenia GWAS https://ogma.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 ]]> Genome-wide association study of retinopathy in individuals without diabetes https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15067 Wed 11 Apr 2018 16:52:00 AEST ]]> Analyzing the role of microRNAs in schizophrenia in the context of common genetic risk variants https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29013 P < 2 × 10−16). Further, the gene set analyses revealed several miRNAs regulating schizophrenia risk genes, with the strongest enrichment for targets of miR-9-5p (P = .0056 for enrichment among the top 1% most-associated single-nucleotide polymorphisms, corrected for multiple testing). It is further of note that MIR9-2 is located in a genomic region showing strong evidence for association with schizophrenia (P = 7.1 × 10−8). The second and third strongest gene set signals were seen for the targets of miR-485-5p and miR-137, respectively. Conclusions and Relevance: This study provides evidence for a role of miR-9-5p in the etiology of schizophrenia. Its implication is of particular interest as the functions of this neurodevelopmental miRNA tie in with established disease biology: it has a regulatory loop with the fragile X mental retardation homologue FXR1 and regulates dopamine D2 receptor density.]]> Wed 11 Apr 2018 15:28:50 AEST ]]> Prediction of breast cancer risk based on profiling with common genetic variants https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28423 Wed 11 Apr 2018 14:49:25 AEST ]]> Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19379 Wed 11 Apr 2018 14:19:24 AEST ]]> Common and low frequency variants in MERTK are independently associated with multiple sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30273 MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients.]]> Wed 11 Apr 2018 13:23:58 AEST ]]> Paracingulate sulcus morphology is associated with hallucinations in the human brain https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22665 Wed 11 Apr 2018 12:37:33 AEST ]]> Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22235 −6). Network analysis of cases and controls sharing haplotypes on chromosome 19 further strengthened the association as there are more large networks of cases sharing haplotypes than controls. This linkage region includes a cluster of zinc finger genes of unknown function. Analysis of genome wide transcriptome data suggests that genes in this zinc finger cluster may be involved in very early developmental regulation of the CNS. Our study also indicates that BEAGLE fastIBD allowed identification of rare variants in large unrelated population with moderate computational intensity. Even with the development of whole-genome sequencing, IBD mapping still may be a promising way to narrow down the region of interest for sequencing priority.]]> Wed 11 Apr 2018 11:41:58 AEST ]]> Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20566 Wed 11 Apr 2018 10:41:17 AEST ]]> Genetic feedback to reduce alcohol consumption in hospital outpatients with risky drinking: feasibility and acceptability https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25770 Wed 11 Apr 2018 10:27:04 AEST ]]> Differential effect of disease-associated ST8SIA2 haplotype on cerebral white matter diffusion properties in schizophrenia and healthy controls https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34987 Tue 03 Sep 2019 18:02:04 AEST ]]> Preliminary analysis of potential drug and gene interactions involving tricyclic antidepressant drugs https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32703 Thu 12 Jul 2018 11:51:28 AEST ]]> Genetic epidemiology studies in hereditary non-polyposis colorectal cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8477 Sat 24 Mar 2018 08:41:59 AEDT ]]> Genetic contribution to all cancers: the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7576 Sat 24 Mar 2018 08:37:24 AEDT ]]> Cohort profile: the Hunter Community Study https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9648 60 years is growing faster than any other age group and is expected to reach 2 billion worldwide by 2050. Internationally and nationally, considerable efforts are being made to promote active ageing. However, Australia lacks the kind of comprehensive longitudinal research underway in Europe and North America. Although Australia does have a number of longitudinal studies designed to address various issues of health and ageing among older adults, only a few of these studies include a broad and comprehensive range of physical and biological measures. The Hunter Community Study (HCS) is a collaborative study between the University of Newcastle’s School of Medicine and Public Health and the Hunter New England Area Health Service. It is a multi disciplinary initiative that was established to fill some existing gaps in ageing research in Australia and is unique in that it has collected detailed information across all six key policy themes as identified in the Framework for an Australian Ageing Research Agenda.]]> Sat 24 Mar 2018 08:35:25 AEDT ]]> Differential proteolytic enzyme activity in eosinophilic and neutrophilic asthma https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1628 99%) was inactivated (and bound to tissue inhibitor of metalloproteinase-1). In neutrophilic asthma, more subjects had NE activity (39%) compared with both healthy control subjects (0%), subjects with eosinophilic asthma (6%), or subjects with paucigranulocytic asthma (0%, p < 0.05). There were strong and consistent positive correlations between interleukin-8, neutrophils, and proteolytic enzymes. MMP-9 was inversely correlated with NE (r = –0.93). Conclusions: Proteolytic enzyme activity in asthma is dependent on the underlying inflammatory phenotype and is differentially regulated with MMP-9 activity a feature of eosinophilic inflammation, and active NE in neutrophilic inflammation.]]> Sat 24 Mar 2018 08:30:34 AEDT ]]> Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13924 −11, odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 x 10−9, OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 x 10−12, OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings1. The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.]]> Sat 24 Mar 2018 08:24:48 AEDT ]]> Sifting the wheat from the chaff: prioritizing GWAS results by identifying consistency across analytical methods https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:12709 Sat 24 Mar 2018 08:16:20 AEDT ]]> Australian schizophrenia research bank: a database of comprehensive clinical, endophenotypic and genetic data for aetiological studies of schizophrenia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10415 Sat 24 Mar 2018 08:12:38 AEDT ]]> Impact of COX-2 rs5275 and rs20417 and GPIIIa rs5918 polymorphisms on 90-day ischemic stroke functional outcome: a novel finding https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17291 Sat 24 Mar 2018 08:01:50 AEDT ]]> Concordance between direct and imputed APOE genotypes using 1000 genomes data https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19672 Sat 24 Mar 2018 08:01:12 AEDT ]]> Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20501 Sat 24 Mar 2018 07:59:03 AEDT ]]> Gastrointestinal polyps in McCune Albright syndrome https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17903 Sat 24 Mar 2018 07:56:40 AEDT ]]> Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20582 Sat 24 Mar 2018 07:55:36 AEDT ]]> First recurrent large genomic rearrangement in the BRCA1 gene found in Poland https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21290 BRCA1 gene increases the risk of the person developing breast and/or ovarian cancer. The prevalence and spectrum of large genomic rearrangements (LGRs) varies considerably among different tested populations. In our previous study we described three LGRs in BRCA1 (exons 13-19, exon 17 and exon 22) in Polish families at high risk of breast and ovarian cancer. In this study we analyzed a group of 550 unselected women with ovarian cancer for the three previously identified LGRs. We used a rapid, single-step and closed-tube method: high-resolution melting analysis (HRMA). In this group of unrelated patients diagnosed with ovarian cancer we found three cases with the same deletions of exon 22. This is the first recurrent large deletion in BRCA1 found in Poland. We conclude that screening for the exon 22 deletion in BRCA1 should be included in the Polish BRCA1 genetic testing panel and possibly extended into other Slavic populations.]]> Sat 24 Mar 2018 07:54:36 AEDT ]]> The CYP27B1 variant associated with an increased risk of autoimmune disease is underexpressed in tolerizing dendritic cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19680 Sat 24 Mar 2018 07:53:39 AEDT ]]> Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5093 Sat 24 Mar 2018 07:48:50 AEDT ]]> Low prevalence of CDKN2A/ARF mutations among early-onset cancers of breast, pancreas and malignant melanoma in Poland https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5178 g), a novel intronic change IVS1+36 g>c and two common variants A148T and IVS3+29 c>g. The results of this study revealed a paucity of mutations in CDKN2A/ARF suggesting that in the Polish population this gene does not contribute significantly to early-onset breast cancer, pancreatic cancer and malignant melanoma.]]> Sat 24 Mar 2018 07:47:42 AEDT ]]> MLH1 Germline Epimutations as a Factor in Hereditary Nonpolyposis Colorectal Cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:286 Sat 24 Mar 2018 07:42:49 AEDT ]]> Evidence for genetic overlap between schizophrenia and age at first birth in women. https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29862 2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014. Conclusions and Relevance: This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers.]]> Sat 24 Mar 2018 07:40:47 AEDT ]]> Development of an experimental model for assessing the effects of cigarette smoke and virus infections on inflammatory responses to bacterial antigens https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28578 Sat 24 Mar 2018 07:35:50 AEDT ]]> KRAS mutation testing in colorectal cancer: the model for molecular pathology testing in the future https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28574 Sat 24 Mar 2018 07:35:50 AEDT ]]> Schizophrenia risk from complex variation of complement component 4 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30050 Sat 24 Mar 2018 07:31:15 AEDT ]]> Association of forced vital capacity with the developmental gene NCOR2 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29806 p<0.002; 0.05/25), with a nominal p-value considered as suggestive evidence. For SNPs with evidence of replication, effects on the expression levels of nearby genes in lung tissue were tested in 1,111 lung samples (Lung eQTL consortium), with further functional investigation performed using public epigenomic profiling data (ENCODE). Results: NCOR2-rs12708369 showed strong replication in children (p = 0.0002), with replication unavailable in adults due to low imputation quality. This intronic variant is in a strong transcriptional enhancer element in lung fibroblasts, but its eQTL effects could not be tested due to low imputation quality in the eQTL dataset. SERPINE2-rs6754561 replicated at nominal level in both adults (p = 0.036) and children (p = 0.045), while WNT16-rs2707469 replicated at nominal level only in adults (p = 0.026). The eQTL analyses showed association of WNT16-rs2707469 with expression levels of the nearby gene CPED1.We found no statistically significant eQTL effects for SERPINE2-rs6754561. Conclusions: We have identified a new gene, NCOR2, in the retinoic acid signalling pathway pointing to a role of vitamin A metabolism in the regulation of FVC. Our findings also support SERPINE2, a COPD gene with weak previous evidence of association with FVC, and suggest WNT16 as a further promising candidate.]]> Sat 24 Mar 2018 07:30:34 AEDT ]]> The VEGF_936_C > T 3 ' UTR polymorphism reduces BRCA1-associated breast cancer risk in Polish women https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4736 T polymorphism in the VEGF gene and its association with sporadic breast cancer risk has been analyzed in various studies yielding conflicting results. To analyze the role of this polymorphism in modifying hereditary breast and ovarian cancer risks, we conducted a case-control study and genotyped 755 Polish BRCA1 carriers, including 319 breast cancer cases, 146 ovarian cancer cases, and 290 unaffected controls. The results revealed an association of the CT + TT genotypes with a reduced breast cancer risk (ORadj 0.63, 95% CI, 0.41-0.98; ORclustered 0.63, 95% CI, 0.48-0.83), and a potential effect on ovarian cancer risk (ORadj 0.62, 95% CI, 0.33-1.18; ORclustered 0.62, 95% CI, 0.47-0.83). Thus, the 936_C>T polymorphism appears to modify disease risks in BRCA1 carriers.]]> Sat 24 Mar 2018 07:21:09 AEDT ]]> Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24832 Sat 24 Mar 2018 07:15:11 AEDT ]]> The effect of a muscarinic receptor 1 gene variant on grey matter volume in schizophrenia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22690 A single nucleotide polymorphism (rs2067477) within the cholinergic muscarinic M1 receptor (CHRM1) perform less well on the Wisconsin Card Sorting Test (WCST) than those who are heterozygous. This study sought to determine whether variation in the rs2067477 genotype was associated with differential changes in brain structure. Data from 227 patients with established schizophrenia or schizoaffective disorder were obtained from the Australian Schizophrenia Research Bank. Whole-brain voxel-based morphometry was performed to compare regional grey matter volume (GMV) between the 267C/C (N=191) and 267C/A (N=36) groups. Secondary analyses tested for an effect of genotype on cognition (the WCST was not available). Individuals who were homozygous (267C/C) demonstrated significantly reduced GMV in the right precentral gyrus compared to those who were heterozygous (267C/A). These preliminary results suggest that the rs2067477 genotype is associated with brain structure in the right precentral gyrus in individuals with schizophrenia/schizoaffective disorder. Future studies are required to replicate these results and directly link the volumetric reductions with specific cognitive processes.]]> Sat 24 Mar 2018 07:11:11 AEDT ]]> A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24704 85% loss of 'pore' function of the P2X7 receptor measured by ATP-induced ethidium uptake. Analysis shows Arg307Gln always occurred with 270His suggesting a single 307Gln-270His haplotype which confers dominant negative effects on P2X7 function and protection against MS. Modelling based on the homologous zP2X4 receptor showed Arg307 is located in a region rich in basic residues located only 12Å from the ligand binding site. Our data show the protective effect against MS of a rare genetic variant of P2RX7 with heterozygotes showing near absent proinflammatory 'pore' function.]]> Sat 24 Mar 2018 07:10:52 AEDT ]]> Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32383 20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10 -5 ) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.]]> Mon 23 Sep 2019 12:09:41 AEST ]]> Health and ageing data from the Hunter Community Study, NSW, Australia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8539 Mon 23 Sep 2019 11:55:24 AEST ]]> Potential simple and multifactorial drug-gene interactions of tricyclic antidepressants in older Australians https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32298 Mon 23 Sep 2019 11:17:56 AEST ]]> Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24831 -8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ~11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.]]> Mon 11 Mar 2019 12:13:11 AEDT ]]> Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33058 Fri 24 Aug 2018 12:08:44 AEST ]]>