| 1. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 2. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 3. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 4. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 5. |
- Fachrizal, Reza, 1993-, et al.
(författare)
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Smart charging of electric vehicles considering photovoltaic power production and electricity consumption : a review
- 2020
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Ingår i: eTransporation. - : Elsevier. - 2590-1168. ; 4
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Forskningsöversikt (refereegranskat)abstract
- Photovoltaics (PV) and electric vehicles (EVs) are two emerging technologies often considered as cornerstones in the energy and transportation systems of future sustainable cities. They both have to be integrated into the power systems and be operated together with already existing loads and generators and, often, into buildings, where they potentially impact the overall energy performance of the buildings. Thus, a high penetration of both PV and EVs poses new challenges. Understanding of the synergies between PV, EVs and existing electricity consumption is therefore required. Recent research has shown that smart charging of EVs could improve the synergy between PV, EVs and electricity consumption, leading to both technical and economic advantages. Considering the growing interest in this field, this review paper summarizes state-of-the-art studies of smart charging considering PV power production and electricity consumption. The main aspects of smart charging reviewed are objectives, configurations, algorithms and mathematical models. Various charging objectives, such as increasing PV utilization and reducing peak loads and charging cost, are reviewed in this paper. The different charging control configurations, i.e., centralized and distributed, along with various spatial configurations, e.g., houses and workplaces, are also discussed. After that, the commonly employed optimization techniques and rule-based algorithms for smart charging are reviewed. Further research should focus on finding optimal trade-offs between simplicity and performance of smart charging schemes in terms of control configuration, charging algorithms, as well as the inclusion of PV power and load forecast in order to make the schemes suitable for practical implementations.
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| 6. |
- Tønnesen, Siren, et al.
(författare)
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Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder : A Multisample Diffusion Tensor Imaging Study
- 2020
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 2451-9022 .- 2451-9030. ; 5:12, s. 1095-1103
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, patients with BD, and healthy control (HC) subjects across 10 cohorts.METHODS: We trained 6 cross-validated models using different combinations of DTI data from 927 HC subjects (18-94 years of age) and applied the models to the test sets including 648 patients with SZ (18-66 years of age), 185 patients with BD (18-64 years of age), and 990 HC subjects (17-68 years of age), estimating the brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results.RESULTS: Tenfold cross-validation revealed high accuracy for all models. Compared with HC subjects, the model including all feature sets significantly overestimated the age of patients with SZ (Cohen's d = -0.29) and patients with BD (Cohen's d = 0.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy-based models showed larger group differences than the models based on other DTI-derived metrics.CONCLUSIONS: Brain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.
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| 7. |
- van der Meer, Dennis, et al.
(författare)
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Clear-sky index space-time trajectories from probabilistic solar forecasts : Comparing promising copulas
- 2020
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Ingår i: Journal of Renewable and Sustainable Energy. - : AMER INST PHYSICS. - 1941-7012. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Short-term probabilistic solar forecasts are an important tool in decision-making processes in which uncertainty plays a non-negligible role. Purely statistical models that produce temporal or spatiotemporal probabilistic solar forecasts are generally trained individually, and the combined forecasts therefore lack the temporal or spatiotemporal correlation present in the data. To recover the spatiotemporal dependence structure, a copula can be employed, which constructs a multivariate distribution from which spatially and temporally correlated uniform random numbers can be sampled, which in turn can be used to generate the so-called space-time trajectories via the inverse probability integral transform. In this study, we employ the recently introduced ultra-fast preselection algorithm to leverage the spatiotemporal information present in a pyranometer network and compare its accuracy to that of quantile regression forecasts that only consider temporal information. We show that the preselection algorithm improves both the calibration and sharpness of the predictive distributions. Furthermore, we employ four copulas, i.e., (1) Gaussian, (2) Student-t, (3) Clayton, and (4) empirical, to generate space-time trajectories. The results highlight the necessity to rigorously assess the calibration of the space-time trajectories and the correct modeling of the spatiotemporal dependence structure, which we show through techniques introduced in atmospheric sciences. The code used to generate the results in this study can be found at https://github.com/DWvanderMeer/SpaceTimeTrajectories.
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| 8. |
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| 9. |
- van der Meer, Dennis, 1988-
(författare)
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Spatio-temporal forecasting and optimization for integration of solar energy in urban energy systems
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The increasing penetration of non-dispatchable renewable energy sources such as photovoltaic (PV) systems in the electricity generating mix poses challenges to the operational performance of the power system. On the demand side, advanced schemes that increase the flexibility of customer loads and the increase in electrification are set to noticeably alter electricity demand. Moreover, a rooftop-mounted PV system alters the electricity demand of the building it is connected to because the generated electricity first serves the electrical loads of the building, thereby affecting the so-called net load that the electricity grid experiences. This thesis studies solutions that enhance the integration of dispersed solar PV power into the power system, with a particular focus on probabilistic and multivariate forecasts and a control framework based on such forecasts. In addition, the thesis evaluates voltage control by means of reactive power control of solar PV inverters. Probabilistic solar, load and net load forecasts are generated using static and dynamic forecast models, where the latter result in approximately 99% less computation time and improved calibration and sharpness but lower forecast resolution. The dynamic forecast models are subsequently used to study the impact of spatial aggregation of customers on the predictive densities, which results in improved calibration and sharpness. Interestingly, the positive effects are already noticeable when aggregating a few customers and this can lead to improved decision-making on the community level. Multivariate forecasts in the form of time and space-time trajectories are also studied, where the multivariate distribution is represented by a copula. Specifically, it is shown that an empirical copula is particularly suitable for high-dimensional spatio-temporal forecasts whereas a Gaussian copula is well suited for temporal forecasts with a large forecast horizon. Furthermore, the thesis develops an augmented version of the scenario-based stochastic model predictive control algorithm that implements the global optimal control action---if it exists---rather than the expectation of independent optimal control actions, which manages forecast errors more effectively. Finally, a population based search method is applied to reactive power control that is able to explicitly and independently model the spatial and temporal relationship between dispersed solar PV inverters, resulting in an improved voltage profile with a smaller population compared to benchmarks. In summary, the thesis demonstrates that forecasts can be improved using several methods, e.g., by spatially aggregating customers, by combining PV power generation and electricity use, by preselecting informative predictors or by postprocessing the forecasts. In turn, the improved accuracy of the forecasts can increase their value in applications such as optimal control problems, that can improve solar PV integration in urban energy systems.
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| 10. |
- Yang, Dazhi, et al.
(författare)
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Probabilistic solar forecasting benchmarks on a standardized dataset at Folsom, California
- 2020
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Ingår i: Solar Energy. - : Elsevier BV. - 0038-092X .- 1471-1257. ; 206, s. 628-639
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Tidskriftsartikel (refereegranskat)abstract
- The present paper echos a recent data article, "A comprehensive dataset for the accelerated development and benchmarking of solar forecasting methods" [J. Renewable Sustainable Energy 11, 036102 (2019)]. The carefully composed dataset by Pedro, Larson, and Coimbra (PLC) presents a rare opportunity for solar forecasters to develop transparent and reproducible algorithms that can bring incremental contributions to the field. In their original paper, data from four different sources, namely, ground-based measurements, sky-camera images, satellite-imagery features, and numerical weather prediction outputs, were arranged in a machine-learning-ready setup. Subsequently, several benchmarks for deterministic forecasting were set forth, for intra-hour, intra-day, and day-ahead scenarios. Nonetheless, a weather forecast is intrinsically five-dimensional, spanning space, time, and probability. In this regard, five reference methods for probabilistic forecasting: (1) complete-history persistence ensemble, (2) Markov-chain mixture model, (3) ordinary least squares, (4) analog ensemble, and (5) quantile regression, are applied to the PLC dataset. The R code provided in this paper follows the structure of the original Python code precisely, facilitating those solar forecasters who are not familiar with Python but have a statistics background.
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