| 1. |
- Roselli, Carolina, et al.
(författare)
-
Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
-
Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
|
|
| 2. |
- Tragante, Vinicius, et al.
(författare)
-
Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
|
|
| 3. |
- Asselbergs, Folkert W., et al.
(författare)
-
Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
|
|
| 4. |
- Di Napoli, Claudia, et al.
(författare)
-
ERA5-HEAT : A global gridded historical dataset of human thermal comfort indices from climate reanalysis
- 2021
-
Ingår i: Geoscience Data Journal. - : John Wiley & Sons. - 2049-6060. ; 8:1, s. 2-10
-
Tidskriftsartikel (refereegranskat)abstract
- The mean radiant temperature (MRT) and the Universal Thermal Climate Index (UTCI) are widely used as human biometeorology parameters to assess the linkages between outdoor environment and human well-being. Historically computed from meteorological station measurements, we here present ERA5-HEAT (Human thErmAl comforT), the first historical dataset of MRT and UTCI as spatially gridded records at the global scale. Derived using climate variables from ERA5, a quality-controlled reanalysis produced by the European Centre for Medium-Range Weather Forecasts (ECMWF) within the Copernicus Climate Change Service (C3S), ERA5-HEAT consists of hourly gridded maps of MRT and UTCI at 0.25 degrees x 0.25 degrees spatial resolution. It currently spans from 1979 to present, and it will be extended in time as updates of ERA5 are made available. ERA5-HEAT provides two streams, a consolidated and an intermediate one, that are released at 2 or 3 months and 5 days behind real time, respectively. Data are publicly and freely available for download at the Climate Data Store which has been developed as part of C3S. Being the only existing global historical gridded time series of MRT and UTCI to date, ERA5-HEAT is aimed at a wide range of end users, from scientists to policymakers, with an interest in environment-health applications at any spatial and temporal scale.
|
|
| 5. |
- Ganesh, Santhi K., et al.
(författare)
-
Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
|
|
| 6. |
- Harrigan, Shaun, et al.
(författare)
-
GloFAS-ERA5 operational global river discharge reanalysis 1979-present
- 2020
-
Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 12:3, s. 2043-2060
-
Tidskriftsartikel (refereegranskat)abstract
- Estimating how much water is flowing through rivers at the global scale is challenging due to a lack of observations in space and time. A way forward is to optimally combine the global network of earth system observations with advanced numerical weather prediction (NWP) models to generate consistent spatio-temporal maps of land, ocean, and atmospheric variables of interest, which is known as a reanalysis. While the current generation of NWP models output runoff at each grid cell, they currently do not produce river discharge at catchment scales directly and thus have limited utility in hydrological applications such as flood and drought monitoring and forecasting. This is overcome in the Global Flood Awareness System (GloFAS; http://www.globalfloods.eu/, last access: 28 June 2020) by coupling surface and sub-surface runoff from the Hydrology Tiled ECMWF Scheme for Surface Exchanges over Land (HTESSEL) land surface model used within ECMWF's latest global atmospheric reanalysis (ERA5) with the LISFLOOD hydrological and channel routing model. The aim of this paper is to describe and evaluate the GloFAS-ERA5 global river discharge reanalysis dataset launched on 5 November 2019 (version 2.1 release). The river discharge reanalysis is a global gridded dataset with a horizontal resolution of 0.1 degrees at a daily time step. An innovative feature is that it is produced in an operational environment so is available to users from 1 January 1979 until near real time (2 to 5 d behind real time). The reanalysis was evaluated against a global network of 1801 daily river discharge observation stations. Results found that the GloFAS-ERA5 reanalysis was skilful against a mean flow benchmark in 86% of catchments according to the modified Kling-Gupta efficiency skill score, although the strength of skill varied considerably with location. The global median Pearson correlation coefficient was 0.61 with an interquartile range of 0.44 to 0.74. The long-term and operational nature of the GloFAS-ERA5 reanalysis dataset provides a valuable dataset to the user community for applications ranging from monitoring global flood and drought conditions to the identification of hydroclimatic variability and change and as raw input for post-processing and machine learning methods that can add further value. The dataset is openly available from the Copernicus Climate Change Service Climate Data Store: https://cds.climate.copernicus.eu/cdsapp#!/dataset/cems-glofas-historical?tab=overview (last access: 28 June 2020) with the following DOI: https://doi.org/10.24381/cds.a4fdd6b9 (C3S, 2019).
|
|
| 7. |
- Matthews, Gwyneth, et al.
(författare)
-
Evaluating the impact of post-processing medium-range ensemble streamflow forecasts from the European Flood Awareness System
- 2022
-
Ingår i: Hydrology and Earth System Sciences. - : Copernicus Publications. - 1027-5606 .- 1607-7938. ; 26:11, s. 2939-2968
-
Tidskriftsartikel (refereegranskat)abstract
- Streamflow forecasts provide vital information to aid emergency response preparedness and disaster risk reduction. Medium-range forecasts are created by forcing a hydrological model with output from numerical weather prediction systems. Uncertainties are unavoidably introduced throughout the system and can reduce the skill of the streamflow forecasts. Post-processing is a method used to quantify and reduce the overall uncertainties in order to improve the usefulness of the forecasts. The post-processing method that is used within the operational European Flood Awareness System is based on the model conditional processor and the ensemble model output statistics method. Using 2 years of reforecasts with daily timesteps, this method is evaluated for 522 stations across Europe. Post-processing was found to increase the skill of the forecasts at the majority of stations in terms of both the accuracy of the forecast median and the reliability of the forecast probability distribution. This improvement is seen at all lead times (up to 15 d) but is largest at short lead times. The greatest improvement was seen in low-lying, large catchments with long response times, whereas for catchments at high elevation and with very short response times the forecasts often failed to capture the magnitude of peak flows. Additionally, the quality and length of the observational time series used in the offline calibration of the method were found to be important. This evaluation of the post-processing method, and specifically the new information provided on characteristics that affect the performance of the method, will aid end users in making more informed decisions. It also highlights the potential issues that may be encountered when developing new post-processing methods.
|
|
