https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33544 -9). The lead single-nucleotide polymorphism (rs12445022) was also associated with cerebral white matter hyperintensities (OR [95% CI] = 1.10 [1.05-1.16] ; p = 5.3 × 10^-5 ; N = 3,670), but not intracerebral hemorrhage (OR [95% CI] = 0.97 [0.84-1.12] ; p = 0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p = 9.4 × 10^-7) and DNA methylation at probe cg16596957 in whole blood (p = 5.3 × 10^-6). Interpretation: 16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements.]]> Wed 15 Dec 2021 16:10:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27984 Wed 15 Dec 2021 16:06:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33716 Wed 12 Dec 2018 14:03:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52461 Wed 11 Oct 2023 15:01:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16807 -9), and IKZF1 rs1110701 (OR 1.69, CI 1.42–2.02, p = 7.26 x 10^-9). There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05). There were no interactions of risk genotypes with age or sex (P-values >0.2). Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.]]> Wed 11 Apr 2018 16:52:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29536 Wed 11 Apr 2018 15:45:41 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29038 Wed 11 Apr 2018 14:13:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22232 Wed 11 Apr 2018 13:37:53 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18827 Wed 11 Apr 2018 13:01:16 AEST ]]> https://nova.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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30590 Wed 11 Apr 2018 10:46:14 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27386 -9, MIR2113; rs17522122, P=2.55 x 10^-8, AKAP6; rs10119, P=5.67 x 10^-9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 x 10^-6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 x 10^-17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.]]> Wed 11 Apr 2018 09:51:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29040 Wed 07 Jul 2021 12:14:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28231 Wed 01 Aug 2018 14:52:20 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53962 Tue 23 Jan 2024 12:39:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53295 Tue 21 Nov 2023 11:54:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33797 Tue 15 Jan 2019 15:29:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52761 Tue 14 Nov 2023 15:30:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42894 Tue 06 Sep 2022 14:32:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48599 Tue 04 Apr 2023 19:22:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30822 50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.]]> Tue 04 Apr 2023 19:09:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33786 -8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.]]> Thu 30 Mar 2023 15:49:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17481 Sat 24 Mar 2018 08:04:10 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17898 Sat 24 Mar 2018 07:56:18 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:26880 -8). Limitations, Reasons for Caution: The meta-analysis for moderate-to-severe endometriosis included results of moderate-to-severe endometriosis cases from our European data sets and all endometriosis cases from the Japanese data sets, as disease stage information was not available for endometriosis cases in the Japanese data sets. Wider Implications of the Findings: SNP rs6542095 is located ~2.3 kb downstream of the IL1A gene and ~6.9 kb upstream of cytoskeleton-associated protein 2-like (CKAP2L) gene. The IL1A gene encodes the IL1a protein, a member of the interleukin 1 cytokine family which is involved in various immune responses and inflammatory processes. These results provide important replication in an independent Japanese sample and, for the first time, association of the IL1A locus in endometriosis patients of European ancestry. SNPs within the IL1A locus may regulate other genes, but if IL1A is the target, our results provide supporting evidence for a link between inflammatory responses and the pathogenesis of endometriosis. Study Funding/Competing Interest(s): The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.]]> Sat 24 Mar 2018 07:41:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28053 Sat 24 Mar 2018 07:41:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28089 Sat 24 Mar 2018 07:39:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25277 −11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28–1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.]]> Sat 24 Mar 2018 07:38:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29335 Sat 24 Mar 2018 07:34:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30267 n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρˆ| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.]]> Sat 24 Mar 2018 07:33:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27460 −8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.]]> Sat 24 Mar 2018 07:32:44 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28443 Sat 24 Mar 2018 07:29:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28311 Sat 24 Mar 2018 07:27:06 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28356 −9) in a combined discovery and replication set (26 953 samples). This single nucleotide polymorphism (SNP) is located within the RBFOX1 gene which is a neuron-specific splicing factor regulating a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins.]]> Sat 24 Mar 2018 07:25:12 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25354 Sat 24 Mar 2018 07:24:42 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23033 Sat 24 Mar 2018 07:13:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23578 −4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 x 10⁻⁸), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.]]> Sat 24 Mar 2018 07:12:44 AEDT ]]> https://nova.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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30005 Mon 17 Oct 2022 12:06:14 AEDT ]]> https://nova.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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19470 Fri 22 May 2020 16:37:38 AEST ]]>