| 1. |
- Archfield, Stacey A., et al.
(author)
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Accelerating advances in continental domain hydrologic modeling
- 2015
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In: Water resources research. - 0043-1397 .- 1944-7973. ; 51:12, s. 10078-10091
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Journal article (peer-reviewed)abstract
- In the past, hydrologic modeling of surface water resources has mainly focused on simulating the hydrologic cycle at local to regional catchment modeling domains. There now exists a level of maturity among the catchment, global water security, and land surface modeling communities such that these communities are converging toward continental domain hydrologic models. This commentary, written from a catchment hydrology community perspective, provides a review of progress in each community toward this achievement, identifies common challenges the communities face, and details immediate and specific areas in which these communities can mutually benefit one another from the convergence of their research perspectives. Those include: (1) creating new incentives and infrastructure to report and share model inputs, outputs, and parameters in data services and open access, machine-independent formats for model replication or reanalysis; (2) ensuring that hydrologic models have: sufficient complexity to represent the dominant physical processes and adequate representation of anthropogenic impacts on the terrestrial water cycle, a process-based approach to model parameter estimation, and appropriate parameterizations to represent large-scale fluxes and scaling behavior; (3) maintaining a balance between model complexity and data availability as well as uncertainties; and (4) quantifying and communicating significant advancements toward these modeling goals.
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| 2. |
- Couch, Fergus J., et al.
(author)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Journal article (peer-reviewed)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 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<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 similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 3. |
- Evangelou, Evangelos, et al.
(author)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Journal article (peer-reviewed)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 4. |
- Mavaddat, Nasim, et al.
(author)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Journal article (peer-reviewed)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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| 5. |
- Pool, Sandra, et al.
(author)
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Streamflow characteristics from modeled runoff time series importance of calibration criteria selection
- 2017
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In: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 21:11, s. 5443-5457
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Journal article (peer-reviewed)abstract
- Ecologically relevant streamflow characteristics (SFCs) of ungauged catchments are often estimated from simulated runoff of hydrologic models that were originally calibrated on gauged catchments. However, SFC estimates of the gauged donor catchments and subsequently the ungauged catchments can be substantially uncertain when models are calibrated using traditional approaches based on optimization of statistical performance metrics (e.g., Nash-Sutcliffe model efficiency). An improved calibration strategy for gauged catchments is therefore crucial to help reduce the uncertainties of estimated SFCs for ungauged catchments. The aim of this study was to improve SFC estimates from modeled runoff time series in gauged catchments by explicitly including one or several SFCs in the calibration process. Different types of objective functions were defined consisting of the Nash-Sutcliffe model efficiency, single SFCs, or combinations thereof. We calibrated a bucket-type runoff model (HBV-Hydrologiska Byrans Vattenavdelning-model) for 25 catchments in the Tennessee River basin and evaluated the proposed calibration approach on 13 ecologically relevant SFCs representing major flow regime components and different flow conditions. While the model generally tended to underestimate the tested SFCs related to mean and high-flow conditions, SFCs related to low flow were generally overestimated. The highest estimation accuracies were achieved by a SFC-specific model calibration. Estimates of SFCs not included in the calibration process were of similar quality when comparing a multi-SFC calibration approach to a traditional model efficiency calibration. For practical applications, this implies that SFCs should preferably be estimated from targeted runoff model calibration, and modeled estimates need to be carefully interpreted.
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| 6. |
- Vis, Marc, et al.
(author)
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Model Calibration Criteria for Estimating Ecological Flow Characteristics
- 2015
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In: Water. - : MDPI AG. - 2073-4441. ; 7:5, s. 2358-2381
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Journal article (peer-reviewed)abstract
- Quantification of streamflow characteristics in ungauged catchments remains a challenge. Hydrological modeling is often used to derive flow time series and to calculate streamflow characteristics for subsequent applications that may differ from those envisioned by the modelers. While the estimation of model parameters for ungauged catchments is a challenging research task in itself, it is important to evaluate whether simulated time series preserve critical aspects of the streamflow hydrograph. To address this question, seven calibration objective functions were evaluated for their ability to preserve ecologically relevant streamflow characteristics of the average annual hydrograph using a runoff model, HBV-light, at 27 catchments in the southeastern United States. Calibration trials were repeated 100 times to reduce parameter uncertainty effects on the results, and 12 ecological flow characteristics were computed for comparison. Our results showed that the most suitable calibration strategy varied according to streamflow characteristic. Combined objective functions generally gave the best results, though a clear underprediction bias was observed. The occurrence of low prediction errors for certain combinations of objective function and flow characteristic suggests that (1) incorporating multiple ecological flow characteristics into a single objective function would increase model accuracy, potentially benefitting decision-making processes; and (2) there may be a need to have different objective functions available to address specific applications of the predicted time series.
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| 7. |
- Wain, Louise V., et al.
(author)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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In: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Journal article (peer-reviewed)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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