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- Nolte, I. M., et al.
(författare)
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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
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| 4. |
- Evangelou, Evangelos, et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Wain, Louise V., et al.
(författare)
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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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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)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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| 7. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 9. |
- Khosrawi, Farahnaz, et al.
(författare)
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Assessment of the interannual variability and influence of the QBO and upwelling on tracer-tracer distributions of N2O and O3 in the tropical lower stratosphere
- 2013
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 13:7, s. 3619-3641
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Tidskriftsartikel (refereegranskat)abstract
- A modified form of tracer-tracer correlations of N2O and O3 has been used as a tool for the evaluation of atmospheric photochemical models. Applying this method monthly averages of N2O and O3 are derived for both hemispheres by partitioning the data into altitude (or potential temperature) bins and then averaging over a fixed interval of N2O. In a previous study, the method has been successfully applied to the validation of two Chemical Transport Models (CTMs) and one Chemistry-Climate Model (CCM) using 1-year climatology derived from the Odin Sub Millimetre Radiometer (Odin/SMR). However, the applicability of a 1-year climatology of monthly averages of N2O and O3 has been questioned due to the inability of some CCMs to simulate a specific year for the evaluation of CCMs. In this study, satellite measurements from Odin/SMR, the Aura Microwave Limb Sounder (Aura/MLS), the Michelson Interferometer for Passive Atmospheric Sounding on ENVISAT (ENVISAT/MIPAS), and the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere (CRISTA-1 and CRISTA-2) as well as model simulations from the Whole Atmosphere Community Climate Model (WACCM) are considered. By using seven to eight years of satellite measurements derived between 2003 and 2010 from Odin/SMR, Aura/MLS, ENVISAT/MIPAS and six years of model simulations from WACCM the interannual variability of lower stratospheric monthly averages of N2O and O3 is assessed. It is shown that the interannual variability of the monthly averages of N2O and O3 is low and thus can be easily distinguished from model deficiencies. Further, it is investigated why large differences between Odin/SMR observations and model simulations from the Karlsruhe Simulation Model of the Middle Atmosphere (KASIMA) and the atmospheric general circulation model ECHAM5/Messy1 are found for the Northern and Southern Hemisphere tropics (0° to 30° N and 0° to −30° S, respectively). The differences between model simulations and observations are most likely caused by an underestimation of the quasi-biennial oscillation and tropical upwelling by the models as well as due to biases and/or instrument noise from the satellite instruments. Finally, an inter-comparison between Odin/SMR, Aura/MLS, ENVISAT/MIPAS and WACCM was performed. The comparison shows that these data sets are generally in good agreement but that also some known biases of the data sets are clearly visible in the monthly averages, thus showing that this method is not only a valuable tool for model evaluation but also for satellite inter-comparisons.
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| 10. |
- Khosrawi, F., et al.
(författare)
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Assessment of the interannual variability and influence of the QBO and upwelling on tracer-tracer distributions of N2O and O3 in the tropical lower stratosphere
- 2013
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 13:7, s. 3619-3641
-
Tidskriftsartikel (refereegranskat)abstract
- A modified form of tracer-tracer correlations of N2O and O-3 has been used as a tool for the evaluation of atmospheric photochemical models. Applying this method, monthly averages of N2O and O3 are derived for both hemispheres by partitioning the data into altitude (or potential temperature) bins and then averaging over a fixed interval of N2O. In a previous study, the method has been successfully applied to the evaluation of two chemical transport models (CTMs) and one chemistry-climate model (CCM) using a 1 yr climatology derived from the Odin Sub-Millimetre Radiometer (Odin/SMR). However, the applicability of a 1 yr climatology of monthly averages of N2O and O3 has been questioned due to the inability of some CCMs to simulate a specific year for the evaluation of CCMs. In this study, satellite measurements from Odin/SMR, the Aura Microwave Limb Sounder (Aura/MLS), the Michelson Interferometer for Passive Atmospheric Sounding on ENVISAT (ENVISAT/MIPAS), and the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere (CRISTA-1 and CRISTA-2) as well as model simulations from the Whole Atmosphere Community Climate Model (WACCM) are considered. By using seven to eight years of satellite measurements derived between 2003 and 2010 from Odin/SMR, Aura/MLS, ENVISAT/MIPAS and six years of model simulations from WACCM, the interannual variability of lower stratospheric monthly averages of N2O and O3 is assessed. It is shown that the interannual variability of the monthly averages of N2O and O3 is low, and thus can be easily distinguished from model deficiencies. Furthermore, it is investigated why large differences are found between Odin/SMR observations and model simulations from the Karlsruhe Simulation Model of the Middle Atmosphere (KASIMA) and the atmospheric general circulation model ECHAM5/Messy1 for the Northern and Southern Hemisphere tropics (0 degrees to 30 degrees N and 0 degrees to -30 degrees S, respectively). The differences between model simulations and observations are most likely caused by an underestimation of the quasi-biennial oscillation and tropical upwelling by the models as well as due to biases and/or instrument noise from the satellite instruments. A realistic consideration of the QBO in the model reduces the differences between model simulation and observations significantly. Finally, an intercomparison between Odin/SMR, Aura/MLS, ENVISAT/MIPAS and WACCM was performed. The comparison shows that these data sets are generally in good agreement, although some known biases of the data sets are clearly visible in the monthly averages. Nevertheless, the differences caused by the uncertainties of the satellite data sets are sufficiently small and can be clearly distinguished from model deficiencies. Thus, the method applied in this study is not only a valuable tool for model evaluation, but also for satellite data intercomparisons.
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