ORCID Profile
0000-0002-9106-0521
Current Organisations
CSIRO
,
University of Cambridge
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 06-2018
Publisher: CSIRO
Date: 2018
Publisher: Cold Spring Harbor Laboratory
Date: 19-06-2020
DOI: 10.1101/2020.06.16.146803
Abstract: We report a meta-analysis of breast, prostate, ovarian, and endometrial cancer genome-wide association data (effective s le size: 237,483 cases/317,006 controls). This identified 465 independent lead variants ( P ×10 −8 ) across 192 genomic regions. Four lead variants were Mb from previously identified risk loci for the four cancers and an additional 23 lead variant-cancer associations were novel for one of the cancers. Bayesian models supported pleiotropic effects involving at least two cancers at 222/465 lead variants in 118/192 regions. Gene-level association analysis identified 13 shared susceptibility genes ( P .6×10 −6 ) in 13 regions not previously implicated in any of the four cancers and not uncovered by our variant-level meta-analysis. Several lead variants had opposite effects across cancers, including a cluster of such variants in the TP53 pathway. Fifty-four lead variants were associated with blood cell traits and suggested genetic overlaps with clonal hematopoiesis. Our study highlights the remarkable pervasiveness of pleiotropy across hormone-related cancers, further illuminating their shared genetic and mechanistic origins at variant- and gene-level resolution.
Publisher: Cold Spring Harbor Laboratory
Date: 02-07-2021
DOI: 10.1101/2021.06.28.21259290
Abstract: Endometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Data from large endometriosis and EOC genome-wide association meta-analyses were used to estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and major EOC histotypes, and to identify shared susceptibility loci. We estimated a significant genetic correlation (r g ) between endometriosis and clear cell (r g =0.71), endometrioid (r g =0.48) and high-grade serous (r g =0.19) ovarian cancer, all supported by Mendelian randomization analyses. A bivariate meta-analysis identified 28 loci associated with endometriosis and EOC, including two novel risk loci, and 19 with evidence for a single underlying causal variant. Differences in the shared risk suggest different underlying pathways may contribute to the relationship between endometriosis and the different histotypes. Functional annotation using transcriptomic and epigenomic profiles of relevant tissues/cells highlighted several target genes. This comprehensive analysis reveals profound genetic overlap between endometriosis and EOC histotypes with valuable genomic targets for understanding the biological mechanisms linking the diseases.
Publisher: Elsevier BV
Date: 06-0005
Publisher: CSIRO
Date: 2013
Publisher: Elsevier BV
Date: 2014
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 27-04-2021
Publisher: Elsevier BV
Date: 12-2017
Publisher: IEEE
Date: 07-2012
Publisher: MDPI AG
Date: 12-01-2022
DOI: 10.3390/GEOSCIENCES12010037
Abstract: This study assesses potential geological connections between the unconventional petroleum plays in the Beetaloo Sub-basin, regional aquifers in overlying basins, and the near surface water assets in the Beetaloo Sub-basin Northern Territory, Australia. To do so, we built an innovative multi-disciplinary toolbox including multi-physics and multi-depth imaging of the geological formations, as well as the study of potentially active tectonic surface features, which we combined with measurement of the helium content in water s led in the aquifer systems and a comparative analysis of the surface drainage network and fault lineaments orientation. Structures, as well as potential natural active and paleo-fluid or gas leakage pathways, were imaged with a reprocessing and interpretation of existing and newly acquired Beetaloo seismic reflection 2D profiles and magnetic datasets to determine potential connections and paleo-leakages. North to north-northwest trending strike slip faults, which have been reactivated in recent geological history, are controlling the deposition at the edges of the Beetaloo Sub-basin. There are two spring complexes associated with this system, the Hot Spring Valley at the northern edge of the eastern Beetaloo Sub-basin and the Mataranka Springs 10 km north of the western sub-basin. Significant rectangular stream ersions in the Hot Spring Valley also indicates current or recently active tectonics. This suggests that those deep-rooted fault systems are likely to locally connect the shallow unconfined aquifer with a deeper gas or fluid source component, possibly without connection with the Beetaloo unconventional prospective plays. However, the origin and flux of this deeper source is unknown and needs to be further investigated to assess if deep circulation is happening through the identified stratigraphic connections. Few north-west trending post-Cambrian fault segments have been interpreted in prospective zones for dry gas plays of the Velkerri Formation. The segments located in the northern part of the eastern Beetaloo Sub-basin do not show any evidence of modern leakages. The segments located around Elliot, in the south of the eastern Beetaloo Sub-basin, as well as low-quality seismic imaging of potential faults in the central part of the western sub-basin, could have been recently reactivated. They could act as open pathways of fluid and gas leakage, sourced from the unconventional plays, deeper formations of the Beetaloo Sub-basin or even much deeper origin, excluding the mantle on the basis of low 3He/4He ratios. In those areas, the data are sparse and of poor quality further field work is necessary to assess whether such pathways are currently active.
Publisher: Cold Spring Harbor Laboratory
Date: 30-04-2021
DOI: 10.1101/2021.04.26.21254132
Abstract: Germline genetic variants are involved in lung cancer (LC) susceptibility. Previous genome-wide association studies (GWAS) have implicated genes involved in smoking propensity and DNA repair but further work is required to identify additional LC susceptibility variants and to investigate LC disease development dynamics. We have undertaken a family history-based genome-wide association (GWAx) study of LC, analysing 48,843 European cases with a parent/sibling with LC compared to 195,387 controls from the UK Biobank. This was meta-analysed with previously described LC GWAS results. We performed Polygenic Risk Scores (PRS) analyses and further evaluated the PRS influence on the somatic environment in exome (N=736) and genome sequencing (N=61) profiled cohorts. Eight novel loci were identified including DNA repair genes ( CHEK1, MDM4 ), metabolic genes ( CYP1A1 ) and variants that were also associated with smoking propensity, such as both subunits of the neuronal α4β2 nicotinic acetylcholine receptor ( CHRNA4 and CHRNB2) . PRS analysis demonstrated that variants related to eQTLs and/or smoking propensity are enriched for susceptibility variants, including variants below genome-wide significant threshold. PRS of LC variants related to smoking propensity were associated with somatic mutation burden in two case cohorts, with in iduals with higher polygenic genetic risk having increased numbers of somatic mutations in their lung tumours. This study has expanded the number of susceptibility loci linked with LC and provided insights into the molecular mechanisms by which these susceptibility variants contribute to the development of lung cancer.
Publisher: Elsevier BV
Date: 2019
Publisher: Oxford University Press (OUP)
Date: 17-03-2023
DOI: 10.1093/JNCI/DJAD043
Abstract: The shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from 12 cancer genome-wide association studies (GWAS) to quantify pairwise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci. We collected GWAS summary statistics for 12 solid cancers based on 376 759 participants with cancer and 532 864 participants without cancer of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies to discover novel cancer susceptibility loci. Finally, we assessed the extent of variant-specific pleiotropy among cancers at known and newly identified cancer susceptibility loci. We observed widespread but modest genome-wide genetic correlations across cancers. In cross-cancer GWAS and transcriptome-wide association studies, we identified 15 novel cancer susceptibility loci. Additionally, we identified multiple variants at 77 distinct loci with strong evidence of being associated with at least 2 cancer types by testing for pleiotropy at known cancer susceptibility loci. Overall, these results suggest that some genetic risk variants are shared among cancers, though much of cancer heritability is cancer-specific and thus tissue-specific. The increase in statistical power associated with larger s le sizes in cross-disease analysis allows for the identification of novel susceptibility regions. Future studies incorporating data on multiple cancer types are likely to identify additional regions associated with the risk of multiple cancer types.
Publisher: CSIRO
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 06-07-2010
Publisher: Impact Journals, LLC
Date: 31-01-2016
Publisher: Wiley
Date: 29-01-2013
DOI: 10.1002/HYP.9691
Publisher: Elsevier BV
Date: 2018
Publisher: CSIRO
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 19-09-2016
Publisher: Elsevier BV
Date: 05-2013
Publisher: Cold Spring Harbor Laboratory
Date: 09-11-2018
DOI: 10.1101/464446
Abstract: Orho-Melander et al. recently reported that lower low-density lipoprotein cholesterol (LDLC) as predicted by the T-allele of the variant rs12916 in HMGCR is associated with a decreased risk of developing breast cancer [odds ratio (OR) = 0.89 95% confidence interval (CI): 0.82–0.96]. 1 This analysis was embedded in a wider Mendelian randomization (MR) study performed using genotype data from a prospective cohort of 26,589 in iduals that included 16,022 women and 1176 incident breast cancer cases. HMGCR encodes 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the enzyme inhibited by statins. The T-allele of rs12916 is associated with reduced HMGCR expression and therefore, in principle, its effects should be analogous to the effects of lifelong statin administration starting at birth. 2 The MR study of Orho-Melander et al. also found that a genome-wide LDLC score based on 32 independent LDLC-associated single nucleotide polymorphisms (SNPs) was not associated with breast cancer. In light of this finding, they suggest that the protective effect of the rs12916 T-allele on breast cancer may either be specific to LDLC lowering via genetic inhibition of HMGCR or be the result of a distinct mechanism that is regulated by rs12916 and HMGCR .
Publisher: CSIRO
Date: 2018
Publisher: Copernicus GmbH
Date: 04-12-2012
DOI: 10.5194/HESS-16-4557-2012
Abstract: Abstract. Reviews of field studies of groundwater recharge have attempted to investigate how climate characteristics control recharge, but due to a lack of data have not been able to draw any strong conclusions beyond that rainfall is the major determinant. This study has used numerical modelling for a range of Köppen-Geiger climate types (tropical, arid and temperate) to investigate the effect of climate variables on recharge for different soil and vegetation types. For the majority of climate types, the correlation between the modelled recharge and total annual rainfall is weaker than the correlation between recharge and the annual rainfall parameters reflecting rainfall intensity. Under similar soil and vegetation conditions for the same annual rainfall, annual recharge in regions with winter-dominated rainfall is greater than in regions with summer-dominated rainfall. The importance of climate parameters other than rainfall in recharge estimation is highest in the tropical climate type. Mean annual values of solar radiation and vapour pressure deficit show a greater importance in recharge estimation than mean annual values of the daily mean temperature. Climate parameters have the lowest relative importance in recharge estimation in the arid climate type (with cold winters) and the temperate climate type. For 75% of all soil, vegetation and climate types investigated, recharge elasticity varies between 2 and 4 indicating a 20% to 40% change in recharge for a 10% change in annual rainfall. Understanding how climate controls recharge under the observed historical climate allows more informed choices of analogue sites if they are to be used for climate change impact assessments.
Publisher: CSIRO
Date: 2016
Publisher: American Geophysical Union (AGU)
Date: 06-2011
DOI: 10.1029/2011GL047657
Publisher: CSIRO
Date: 2015
Publisher: Wiley
Date: 15-09-2009
DOI: 10.1002/HYP.7445
Publisher: American Association for Cancer Research (AACR)
Date: 30-11-2015
DOI: 10.1158/1078-0432.CCR-15-0632
Abstract: Purpose: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. Experimental Design: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. Results: Five SNPs were significantly associated (P ≤ 1.0 × 10−5) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23), and rs6674079 (1q22), were located in long noncoding RNAs (lncRNAs) RP11-179A10.1, RP11-314O13.1, and RP11-284F21.8, respectively (P ≤ 7.1 × 10−6). ENCODE ChIP-seq data at 1q22 for normal ovary show evidence of histone modification around RP11-284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression and high-density lipoprotein (HDL)-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA ≤6 × 10−3). Conclusions: We have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies. Clin Cancer Res 21(23) 5264–76. ©2015 AACR.
Publisher: Copernicus GmbH
Date: 24-02-2012
Abstract: Abstract. Deep drainage estimates are required for effective management of water resources. However, field measurements are time consuming and costly so simple empirical relationships are often used. Relationships developed between clay content of the surface soil and deep drainage have been used extensively in Australia to provide regional estimates of deep drainage but these relationships have been poorly justified and did not include rainfall in the relationships. Here we present a rigorous appraisal of clay content of soils and rainfall as predictors of deep drainage using an extensive database of field observations from across Australia. This study found that annual average rainfall and the average clay content of the top 2 m of the soil are statistically significant predictors of point scale deep drainage. Relationships have been defined for annual, perennial and tree type vegetation as a line of best fit along with 95% confidence intervals. This allows the uncertainty in these deep drainage estimates to be assessed for the first time.
Publisher: CSIRO
Date: 2011
Publisher: Oxford University Press (OUP)
Date: 02-05-2022
DOI: 10.1093/JNCI/DJAC087
Abstract: Germline genetic variation contributes to lung cancer (LC) susceptibility. Previous genome-wide association studies (GWAS) have implicated susceptibility loci involved in smoking behaviors and DNA repair genes, but further work is required to identify susceptibility variants. To identify LC susceptibility loci, a family history-based genome-wide association by proxy (GWAx) of LC (48 843 European proxy LC patients, 195 387 controls) was combined with a previous LC GWAS (29 266 patients, 56 450 controls) by meta-analysis. Colocalization was used to explore candidate genes and overlap with existing traits at discovered susceptibility loci. Polygenic risk scores (PRS) were tested within an independent validation cohort (1 666 LC patients vs 6 664 controls) using variants selected from the LC susceptibility loci and a novel selection approach using published GWAS summary statistics. Finally, the effects of the LC PRS on somatic mutational burden were explored in patients whose tumor resections have been profiled by exome (n = 685) and genome sequencing (n = 61). Statistical tests were 2-sided. The GWAx–GWAS meta-analysis identified 8 novel LC loci. Colocalization implicated DNA repair genes (CHEK1), metabolic genes (CYP1A1), and smoking propensity genes (CHRNA4 and CHRNB2). PRS analysis demonstrated that these variants, as well as subgenome-wide significant variants related to expression quantitative trait loci and/or smoking propensity, assisted in LC genetic risk prediction (odds ratio = 1.37, 95% confidence interval = 1.29 to 1.45 P & .001). Patients with higher genetic PRS loads of smoking-related variants tended to have higher mutation burdens in their lung tumors. This study has expanded the number of LC susceptibility loci and provided insights into the molecular mechanisms by which these susceptibility variants contribute to LC development.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2017
DOI: 10.1038/NG.3826
Publisher: BMJ
Date: 03-11-2022
Abstract: Heterozygous disruptions of FOXP2 were the first identified molecular cause for severe speech disorder: childhood apraxia of speech (CAS), and yet few cases have been reported, limiting knowledge of the condition. Here we phenotyped 28 in iduals from 17 families with pathogenic FOXP2 -only variants (12 loss-of-function, five missense variants 14 males aged 2 to 62 years). Health and development (cognitive, motor, social domains) were examined, including speech and language outcomes with the first cross-linguistic analysis of English and German. Speech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%), with similar speech presentations across English and German. Speech was still impaired in adulthood, and some speech sounds (eg, ‘th’, ‘r’, ‘ch’, ‘j’) were never acquired. Language impairments (21/25, 84%) ranged from mild to severe. Comorbidities included feeding difficulties in infancy (10/26, 38%), fine (13/26, 50%) and gross (13/26, 50%) motor impairment, anxiety (5/27, 19%), depression (6/27, 22%) and sleep disturbance (10/24, 42%). Physical features were common (22/27, 81%) but with no consistent pattern. Cognition ranged from average to mildly impaired and was incongruent with language ability for ex le, seven participants with severe language disorder had average non-verbal cognition. Although we identify an increased prevalence of conditions like anxiety, depression and sleep disturbance, we confirm that the consequences of FOXP2 dysfunction remain relatively specific to speech disorder, as compared with other recently identified monogenic conditions associated with CAS. Thus, our findings reinforce that FOXP2 provides a valuable entry point for examining the neurobiological bases of speech disorder.
Publisher: American Geophysical Union (AGU)
Date: 09-2007
DOI: 10.1029/2006WR005465
Publisher: Elsevier BV
Date: 10-2020
Publisher: CSIRO
Date: 2016
Publisher: Adelaide, CSIRO
Date: 2007
Publisher: CSIRO
Date: 2015
Publisher: Copernicus GmbH
Date: 25-10-2010
DOI: 10.5194/HESS-14-2023-2010
Abstract: Abstract. Effective management of water resources requires that all elements of the water balance be estimated. Groundwater recharge measurements are difficult, time consuming and expensive. In some cases a field study cannot be justified and simple empirical relationships are used to estimate recharge, and often the value chosen is simply a percentage of rainfall. This paper aims to use a database of 4386 field based estimates of recharge from 172 studies in Australia to produce simple empirical relationships that relate recharge to nationally available datasets and hence can be used to estimate recharge in data-poor areas in a scientifically defensible way. It was found that the vegetation and soil type were critical determinants in forming relationships between average annual rainfall and average annual recharge. Climate zones and surface geology (lithology) were not found to be significant determinants in the relationship between rainfall and recharge. The method used to estimate recharge had an impact upon the magnitude of the recharge estimates due to the spatial and temporal scales over which the different methods estimate recharge. Relationships have been developed here between average annual rainfall and average annual recharge for combinations of soil and vegetation type that can be used with only nationally available datasets to provide a recharge estimate. These relationships can explain 60% of the variance in recharge measurements across Australia. The uncertainty in the recharge estimated using these relationships is generally greater than an order of magnitude. This means that if these relationships are used to help determine water allocations, then the precautionary principle should limit allocations to less than about 5% of the estimated recharge. If allocations are greater than this, a more detailed site specific study is warranted.
Publisher: Springer Science and Business Media LLC
Date: 31-08-2013
Publisher: CSIRO
Date: 2020
DOI: 10.25919/TG90-3X77
Publisher: CSIRO
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 19-01-2017
DOI: 10.1038/BJC.2016.426
Publisher: Canberra, CSIRO Water for a Healthy Country Flagship
Date: 2009
Publisher: Adelaide, CSIRO
Date: 2008
Publisher: Elsevier BV
Date: 06-2018
Publisher: CSIRO
Date: 2010
Publisher: Elsevier BV
Date: 05-2021
Publisher: CSIRO
Date: 2012
Publisher: American Geophysical Union (AGU)
Date: 09-2012
DOI: 10.1029/2011WR011441
Abstract: Overbank flood recharge is increasingly acknowledged as important for estimations of aquifer sustainable yield. The physics of this process in areas with shallow groundwater, however, is not well understood and typically is not included in river or groundwater models. Modeling of the overbank flood recharge process was undertaken using a fully coupled, surface‐subsurface flow model to compare the volume of infiltration through a floodplain with varying surface sediment, aquifer, and flood parameters. The infiltration volume was found to increase with the conductance of the clogging layer (represented by a thin veneer of sediments across the floodplain and river bed), flood wave height, peak duration, and aquifer transmissivity and to decrease with increasing water table gradient (positive toward the river). The influence of the flood wave and aquifer hydraulic parameters was more pronounced in systems with sand or loam clogging layers. Irregularities in floodplain elevation had a large effect on infiltration volume. A dimensionless analysis of the flood recharge process identified the factors that limited flood infiltration for each of the modeled scenarios: the clogging layer conductance, unsaturated aquifer storage, or aquifer transmissivity. A dimensionless number F * was used to predict the limiting factor in floodplain systems. An analytical equation was developed to estimate the infiltration volume for catchments where full numerical modeling is not warranted or applicable. Results from the analytical equation compared favorably with recharge modeled using a more complex numerical model.
Publisher: MDPI AG
Date: 10-09-2019
DOI: 10.3390/W11091879
Abstract: As the largest freshwater storage in the world, groundwater plays an important role in maintaining ecosystems and helping humans adapt to climate change. However, groundwater dynamics, such as groundwater recharge, cannot be measured directly and is influenced by spatially and temporally complex processes, models are therefore required to capture the dynamics and provide scientific advice for decision-making. This paper developed, estimated and compared the performance of linear regression, multi-layer perception (MLP) and Long Short-Term Memory (LSTM) models in predicting groundwater recharge. The experimental dataset consists of time series of annual recharge from the year 1970 to 2012, based on water table fluctuation estimates from 465 bores in the states of South Australia and Victoria, Australia. We identified the factors that influenced groundwater recharge and found that the correlation between rainfall and groundwater recharge was strongest. The linear regression model had the poorest fitting performance, with the root mean squared error (RMSE) being greater than 0.19 when various proportions of training data were considered. The MLP model outperformed the linear regression in the prediction capability, achieving RMSE = 0.11 when 80% of training data was considered. The LSTM model was found to have the best performance, whose root mean squared errors were less than 0.12 when various proportions of training data were applied. The relative importance of influential predictors was evaluated using the above three models.
Publisher: Wiley
Date: 12-2019
DOI: 10.1002/ECO.2172
Publisher: Springer Science and Business Media LLC
Date: 31-07-2007
Publisher: Wiley
Date: 05-08-2019
DOI: 10.1111/GWAT.12923
Abstract: Groundwater responses to barometric pressure fluctuations are characterized using the concept of barometric efficiency (BE). For semiconfined and confined aquifers, BE values can be used to provide efficient, low-cost estimates of specific storage. This study compares, for the first time, eight existing methods of BE estimation. Comparisons were undertaken using data from the Peel region of Western Australia. Fourier analysis and regression deconvolution methods were used to estimate aquifer confinement status. The former approach was found to be robust and provided a quantitative basis for spatial comparisons of the degree of confinement. The latter approach was confounded by the presence of diurnal and/or semidiurnal signals. For wells at which semiconfined or confined responses were identified, frequency and time domain methods were used to estimate BE values. Most BE estimation methods were similarly confounded by diurnal and/or semidiurnal signals, with the exception of the Acworth et al. (2016) method. Specific storage values calculated from BE values were order-of-magnitude consistent with the results of four historical pumping tests. The methods implemented in this research provide efficient, low-cost alternatives to hydraulic testing for estimating aquifer confinement, as well as the BE and specific storage of semiconfined and confined aquifers. The frequency and duration of observations required by these methods are minimal for ex le, typically requiring a minimum of four observations per day over a four month period. In some locations they may allow additional insights to be derived from existing groundwater hydrograph data.
Publisher: Springer Science and Business Media LLC
Date: 2020
Publisher: CSIRO
Date: 2015
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 12-2008
Publisher: Springer Science and Business Media LLC
Date: 23-10-2017
DOI: 10.1038/NG.3785
Publisher: CSIRO
Date: 2021
DOI: 10.25919/4CBW-KK97
Publisher: Cold Spring Harbor Laboratory
Date: 09-11-2018
DOI: 10.1101/464115
Abstract: Observational studies suggest that higher birth weight (BW) is associated with increased risk of breast cancer in adult life. We conducted a two-s le Mendelian randomisation (MR) study to assess whether this association is causal. Sixty independent single nucleotide polymorphisms (SNPs) known to be associated at P 5 × 10 -8 with BW were used to construct (1) a 41-SNP instrumental variable (IV) for univariable MR after removing SNPs with pleiotropic associations with other breast cancer risk factors and (2) a 49-SNP IV for multivariable MR after filtering SNPs for data availability. BW predicted by the 41-SNP IV was not associated with overall breast cancer risk in inverse-variance weighted (IVW) univariable MR analysis of genetic association data from 122,977 breast cancer cases and 105,974 controls (odds ratio = 0.86 per 500 g higher BW 95% confidence interval: 0.73—1.01). Sensitivity analyses using four alternative methods and three alternative IVs, including an IV with 59 of the 60 BW-associated SNPs, yielded similar results. Multivariable MR adjusting for the effects of the 49-SNP IV on birth length, adult height, adult body mass index, age at menarche, and age at menopause using IVW and MR-Egger methods provided estimates consistent with univariable analyses. Results were also similar when all analyses were repeated after restricting to estrogen receptor-positive or -negative breast cancer cases. Point estimates of the odds ratios from most analyses performed indicated an inverse relationship between genetically-predicted BW and breast cancer. Thus, there is little evidence from MR to suggest that the previously observed association between higher BW and increased risk of breast cancer in adult life is causal.
Publisher: CSIRO
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 09-10-2008
Publisher: CSIRO
Date: 2021
DOI: 10.25919/PAZT-J052
Publisher: CSIRO
Date: 2018
Publisher: American Association for Cancer Research (AACR)
Date: 02-2019
DOI: 10.1158/0008-5472.CAN-18-2726
Abstract: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2016
DOI: 10.1038/SREP32512
Abstract: Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92 CI 0.90–0.94 P = 8.96 × 10 −15 )) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10 −09 , r 2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10 −11 , r 2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 09-2018
Publisher: Springer Science and Business Media LLC
Date: 30-12-2020
Publisher: CSIRO
Date: 2018
Publisher: CSIRO
Date: 2020
Publisher: Wiley
Date: 06-2022
DOI: 10.1002/HYP.14625
Abstract: With rising concerns for water security and increasing interest in water resource development, accounting for river transmission losses in arid/semi‐arid region water budgets is a crucial yet challenging task. Transmission losses are usually confounded with many different processes and exacerbated by hydrologic and climatic non‐stationarity. A common deficiency in existing basin‐scale river system loss models is the poor representation of dynamic river losses into groundwater. To address this, a new conceptual model was developed to represent relevant river processes including rainfall to runoff transformation, river loss/gain to groundwater, river rainfall/evaporation and routing on a reach‐by‐reach basis. A critical process of the model is the exchange of water between the river and a groundwater store, called the river bed/bank store. The exchange to groundwater typically occurs with relatively high river volumes. Conversely, the store can discharge water back to the river when river volumes are relatively low. The model is designed to be transposable between different time‐periods, such as pre‐ and post‐development scenarios, assuming sufficient data exist during calibration. Using explicit Bayesian formulations, calibrations were performed against observed streamflow and remotely sensed evapotranspiration data. The new loss model was investigated using a test case in the Cooper Creek, Australia. The model performed overall better than a benchmark (flow vs. loss) model in a range of calibration/validation metrics. The new model provides river state and flux terms typically not available in basin‐scale models, and thus, is expected to be valuable during calibration/validation by allowing the use of alternative observed data types, for ex le, actual evapotranspiration or groundwater observations. Moreover, these extra terms could be very beneficial to water budget and ecological assessment studies.
Publisher: American Geophysical Union (AGU)
Date: 08-2019
DOI: 10.1029/2019WR025285
Publisher: CSIRO
Date: 2011
Publisher: American Association for Cancer Research (AACR)
Date: 04-2018
DOI: 10.1158/1055-9965.EPI-17-0315
Abstract: In this review, we summarize current progress in the genetic epidemiology of epithelial ovarian cancer (EOC), focusing exclusively on elucidating the role of common germline genetic variation in conferring susceptibility to EOC. We provide an overview of the more than 30 EOC risk loci identified to date by genome-wide association studies (GWAS) and describe the contribution of large-scale, cross-cancer type, custom genotyping projects, such as the OncoArray and the Collaborative Oncological Gene-Environment Study, to locus discovery and replication. We discuss the histotype-specific nature of these EOC risk loci, pleiotropy, or overlapping genetic effects between EOC and other hormone-related cancer types, and the application of findings to polygenic risk prediction for EOC. The second part of the article offers a concise review of primarily laboratory-based studies that have led to the identification of several putative EOC susceptibility genes using common variants at the known EOC risk loci as starting points. More global biological insights emerging from network- and pathway-based analyses of GWAS for EOC susceptibility are also highlighted. Finally, we delve into potential future directions, including the need to identify EOC risk loci in non-European populations and the next generation of GWAS functional studies that are likely to involve genome editing to establish the cell type–specific carcinogenic effects of EOC risk variants Cancer Epidemiol Biomarkers Prev 27(4) 395–404. ©2018 AACR. See all articles in this CEBP Focus section, “Genome-Wide Association Studies in Cancer.”
Publisher: Elsevier BV
Date: 06-2012
Publisher: Elsevier BV
Date: 07-2021
Publisher: CSIRO
Date: 2022
DOI: 10.25919/FWYJ-CP80
Publisher: Australian Water Association
Date: 2018
Publisher: CSIRO: Water for a Healthy Country National Research Flagship
Date: 2008
Publisher: Oxford University Press (OUP)
Date: 10-10-2022
DOI: 10.1093/JNCI/DJAC160
Abstract: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer–related cell types. We identified statistically significant risk associations with CNVs at known EOC risk genes BRCA1 (PEOC = 1.60E-21 OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4 odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4 ORHGSOC = 3.31 deletion). Four suggestive associations (P & .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P & .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.
Publisher: CSIRO, National Water Commission (waterline report)
Date: 2010
Publisher: Springer Science and Business Media LLC
Date: 18-03-2021
DOI: 10.1007/S10040-021-02323-1
Abstract: Regional-scale estimates of groundwater recharge are inherently uncertain, but this uncertainty is rarely quantified. Quantifying this uncertainty provides an understanding of the limitations of the estimates, and being able to reduce the uncertainty makes the recharge estimates more useful for water resources management. This paper describes the development of a method to constrain the uncertainty in upscaled recharge estimates using a rejection s ling procedure for baseflow and remotely sensed evapotranspiration data to constrain the lower and upper end of the recharge distribution, respectively. The recharge estimates come from probabilistic chloride mass-balance estimates from 3,575 points upscaled using regression kriging with rainfall, soils and vegetation as covariates. The method is successfully demonstrated for the 570,000-km 2 Cambrian Limestone Aquifer in northern Australia. The method developed here is able to reduce the uncertainty in the upscaled chloride mass-balance estimates of recharge by nearly a third using data that are readily available. The difference between the 5 th and 95 th percentiles of unconstrained recharge across the aquifer was 31 mm/yr (range 5–36 mm/yr) which was reduced to 22 mm/yr for the constrained case (9–31 mm/yr). The spatial distribution of recharge was dominated by the spatial distribution of rainfall but was comparatively reduced in areas with denser vegetation or finer textured soils. Recharge was highest in the north-west in the Daly River catchment with a catchment average of 101 (61–192) mm/yr and lowest in the south-east Georgina River catchment with 6 (4–12) mm/yr.
Publisher: Copernicus GmbH
Date: 18-09-2012
DOI: 10.5194/HESS-16-3341-2012
Abstract: Abstract. The Köppen-Geiger climate classification has been used for over a century to delineate climate types across the globe. As it was developed to mimic the distribution of vegetation, it may provide a useful surrogate for making projections of the future distribution of vegetation, and hence resultant hydrological implications, under climate change scenarios. This paper developed projections of the Köppen-Geiger climate types covering the Australian continent for a 2030 and 2050 climate relative to a 1990 historical baseline climate using 17 Global Climate Models (GCMs) and five global warming scenarios. At the highest level of classification for a +2.4 °C future climate (the upper limit projected for 2050) relative to the historical baseline, it was projected that the area of the continent covered by – tropical climate types would increase from 8.8% to 9.1% – arid climate types would increase from 76.5% to 81.7% – temperate climate types would decrease from 14.7% to 9.2% – cold climate types would decrease from 0.016% to 0.001%. Previous climate change impact studies on water resources in Australia have assumed a static vegetation distribution. If the change in projected climate types is used as a surrogate for a change in vegetation, then the major transition in climate from temperate to arid in parts of Australia under a drier future climate could cause indirect effects on water resources. A transition from annual cropping to perennial grassland would have a compounding effect on the projected reduction in recharge. In contrast, a transition from forest to grassland would have a mitigating effect on the projected reduction in runoff.
Publisher: Australia, CSIRO
Date: 2008
Publisher: CSIRO
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 29-02-2016
DOI: 10.1038/NG.3521
Publisher: Elsevier BV
Date: 2012
Publisher: Wiley
Date: 23-12-2021
Publisher: American Geophysical Union (AGU)
Date: 07-2013
DOI: 10.1002/WRCR.20292
Publisher: CSIRO
Date: 2018
Publisher: Elsevier BV
Date: 06-2018
Publisher: Copernicus GmbH
Date: 03-04-2014
DOI: 10.5194/HESS-18-1273-2014
Abstract: Abstract. Accounting for groundwater recharge from overbank flooding is required to reduce uncertainty and error in river-loss terms and groundwater sustainable-yield calculations. However, continental- and global-scale models of surface water–groundwater interactions rarely include an explicit process to account for overbank flood recharge (OFR). This paper upscales previously derived analytical equations to a continental scale using national soil atlas data and satellite imagery of flood inundation, resulting in recharge maps for seven hydrologically distinct Australian catchments. Recharge for three of the catchments was validated against independent recharge estimates from bore hydrograph responses and one catchment was additionally validated against point-scale recharge modelling and catchment-scale change in groundwater storage. Flood recharge was predicted for four of the seven catchments modelled, but there was also unexplained recharge present from the satellite's flood inundation mapping data. At a catchment scale, recharge from overbank flooding was somewhat under-predicted using the analytical equations, but there was good confidence in the spatial patterns of flood recharge produced. Due to the scale of the input data, there were no significant relationships found when compared at a point scale. Satellite-derived flood inundation data and uncertainty in soil maps were the key limitations to the accuracy of the modelled recharge. Use of this method to model OFR was found to be appropriate at a catchment to continental scale, given appropriate data sources. The proportion of OFR was found to be at least 4% of total change in groundwater storage in one of the catchments for the period modelled, and at least 15% of the riparian recharge. Accounting for OFR is an important, but often overlooked, requirement for closing water balances in both the surface water and groundwater domains.
Publisher: CSIRO
Date: 2017
Publisher: CSIRO
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 27-04-2016
DOI: 10.1038/NCOMMS11375
Abstract: Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations ( P × 10 −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 .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.
Publisher: Modelling and Simulation Society of Australia and New Zealand
Date: 08-2023
Publisher: Elsevier BV
Date: 03-2008
Publisher: Elsevier BV
Date: 03-2007
Publisher: American Geophysical Union (AGU)
Date: 02-2013
DOI: 10.1002/WRCR.20123
Publisher: Elsevier BV
Date: 12-2014
Publisher: Springer Science and Business Media LLC
Date: 19-11-2012
Publisher: CSIRO
Date: 2012
Publisher: CSIRO Water for a Healthy Country
Date: 2012
Publisher: CSIRO
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 06-07-2010
Publisher: Wiley
Date: 17-06-2016
DOI: 10.1002/IJC.30150
Publisher: CSIRO
Date: 2020
Publisher: CSIRO Publishing
Date: 2013
DOI: 10.1071/SR13090
Abstract: Riverbed hydraulic conductivity (Kr) was measured along one river reach in four tributaries of the Murray–Darling Basin (MDB) in south-eastern Australia. Two techniques were trialled: in-river falling-head tests in high Kr sediments, and laboratory evaporation tests on intact riverbed cores for low Kr sediments. In-river falling-head tests were conducted using two types of permeameter: a steel-base permeameter or a stand-pipe permeameter. Kr was found to range from 10–10 to 10–3 m s–1, corresponding to a range in riverbed sediment textures from clay to silty gravels, respectively. Although the within-reach variability in Kr was also large, in general the river reaches could be ided in two groups, those with a low Kr ( –8 m s–1) or a high Kr ( –5 m s–1). The low Kr reach (Billabong Creek) was a clay-lined bed, whereas the others had silty sand or silty gravel beds. Thus, regional-scale assessments of Kr in the MDB could be made using a stratified s ling process in which reaches would be first classified into low or high Kr classes, and then Kr measurements made in a subs le of low and high Kr reaches. This would be an improvement over the current practice whereby riverbed Kr is estimated either from regional soil maps or through the calibration of groundwater models.
Publisher: Springer Science and Business Media LLC
Date: 11-2015
Publisher: Impact Journals, LLC
Date: 03-03-2017
Publisher: Springer Science and Business Media LLC
Date: 23-10-2017
DOI: 10.1038/NATURE24284
Publisher: Wiley
Date: 03-11-2023
DOI: 10.1002/ECO.2490
Abstract: Rivers in arid regions often rely on flow generated from wetter regions upstream, leading to high transmission losses of downstream flows. These transmission losses support a range of ecosystems, but partitioning the volume of the transmission losses across the floodplain, riparian zone and in‐channel is difficult. This study presents a methodology relying primarily on multi‐decade satellite remotely sensed actual evapotranspiration estimates to partition these losses. The method was applied to the ~40,000 km 2 floodplain of Cooper Creek in the central Australian arid zone, where first, the alluvial landscape was classified based on actual evapotranspiration rates, and second, both regional‐ (i.e., for the entire floodplain) and local‐scale (i.e., for each waterhole) water balances were calculated to partition these losses. Regional‐scale results estimated that 82% of transmission losses occurred on the floodplain, 13% in the riparian zone and 5% from open water in the river channel and waterholes. These results showed that a refinement of the conceptual model of recharge from the waterholes is necessary as vast areas of the riparian zone are likely to be accessing a shallow freshwater lens rather than a discrete freshwater lens below the permanent waterholes. This method can be used in other data‐poor arid river systems as it uses globally accessible data sources.
Publisher: CSIRO
Date: 2020
DOI: 10.25919/WX1P-A027
Publisher: Elsevier BV
Date: 09-2005
Publisher: CSIRO
Date: 2018
Publisher: Elsevier BV
Date: 07-2021
Publisher: CSIRO
Date: 2011
Publisher: CSIRO
Date: 2011
Publisher: CSIRO
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 21-06-2016
Publisher: Elsevier BV
Date: 06-2005
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Russell Crosbie.