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- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 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
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 2. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 5. |
- Alnaes, Dag, et al.
(författare)
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Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk
- 2019
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Ingår i: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X. ; 76:7, s. 739-748
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceBetween-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. ObjectivesTo compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and ParticipantsThis case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and MeasuresMean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. ResultsA comparison of 1151 patients with schizophrenia (mean [SD] age,33.8[10.6] years; 68.6% male [n=790] and 31.4% female [n=361]) with 2010 healthy controls (mean [SD] age,32.6[10.4] years; 56.0% male [n=1126] and 44.0% female [n=884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34), cortical (t=3.24) and ventricle (t range, 3.15-5.78) volumes, and hippocampal subfields (t range, 2.32-3.55). In the UK Biobank sample of 12 490 participants (mean [SD] age,55.9 [7.5] years; 48.2% male [n=6025] and 51.8% female [n=6465]), higher PRS was associated with thinner frontal and temporal cortices and smaller left CA2/3 (t=-3.00) but was not significantly associated with dispersion. Conclusions and RelevanceThis study suggests that schizophrenia is associated with substantial brain structural heterogeneity beyond the mean differences. These findings may reflect higher sensitivity to environmental and genetic perturbations in patients, supporting the heterogeneous nature of schizophrenia. A higher PRS was associated with thinner frontotemporal cortices and smaller hippocampal subfield volume, but not heterogeneity. This finding suggests that brain variability in schizophrenia results from interactions between environmental and genetic factors that are not captured by the PRS. Factors contributing to heterogeneity in frontotemporal cortices and hippocampus are key to furthering our understanding of how genetic and environmental factors shape brain biology in schizophrenia.
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| 7. |
- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 8. |
- Munkhammar, Joakim, 1982-, et al.
(författare)
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Probabilistic forecasting of high-resolution clear-sky index time-series using a Markov-chain mixture distribution model
- 2019
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Ingår i: Solar Energy. - : Elsevier BV. - 0038-092X .- 1471-1257. ; 184, s. 688-695
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Tidskriftsartikel (refereegranskat)abstract
- This study presents a Markov-chain mixture (MCM) distribution model for forecasting the clear-sky index-normalized global horizontal irradiance. The model is presented in general, but applied to, and tested or minute resolution clear-sky index data for the two different climatic regions of Norrkoping, Sweden, and Hawaii USA. Model robustness is evaluated based on a cross-validation procedure and on that basis a reference con figuration of parameter settings for evaluating the model performance is obtained. Simulation results ar compared with persistence ensemble (PeEn) and quantile regression (QR) model simulations for both data set and for D = 1,...,5 steps ahead forecasting scenarios. The results are evaluated by a set of probabilistic fore casting metrics: reliability mean absolute error (reliability MAE), prediction interval normalized average widti (PINAW), continuous ranked probability score (CRPS) and continuous ranked probability skill score (skill). Botl in terms of reliability MAE and CRPS, the MCM model outperforms PeEn for all simulated scenarios. In terms c reliability MAE, the QR model outperforms the MCM model for most simulated scenarios. However, in terms c mean CRPS, the MCM model outperforms the QR model in most simulated scenarios. A point forecasting esti mate is also provided. The MCM model is concluded to be a computationally inexpensive, accurate and pars meter insensitive probabilistic model. Based on this, it is suggested as a candidate benchmark model in prop abilistic forecasting, in particular for solar irradiance forecasting. For applicability, a Python script of the MCA model is available as SheperoMah/MCM-distribution-forecasting at GitHub.
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| 9. |
- Munkhammar, Joakim, 1982-, et al.
(författare)
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Probabilistic forecasting of the clear-sky index using Markov-chain mixture distribution and copula models
- 2019
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Ingår i: 2019 Ieee 46Th Photovoltaic Specialists Conference (PVSC). - New York : IEEE. - 9781728104942 ; , s. 2428-2433
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Konferensbidrag (refereegranskat)abstract
- Two probabilistic forecasting models for the clear-sky index, based on the Markov-chain mixture distribution (MCM) and copula clear-sky index generators, are presented and evaluated. In terms of performance, these models are compared with two benchmark models: a Quantile Regression (QR) model and the Persistence Ensemble (PeEn). The models are tested on minute resolution clear-sky index data, which was estimated from irradiance data for two different climatic regions: Hawaii, USA and Norrkoping, Sweden. Results show that the copula model generally outperforms the PeEn, while the MCM and QR models are superior in all tested aspects. Comparing MCM and QR reliability, the QR is superior, while the MCM is superior in mean CRPS and skill score. The MCM model is proposed as a potential benchmark for probabilistic solar forecasting. The MCM model is available in Python as SheperoMah/MCM-distribution-forecasting at GitHub.
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| 10. |
- Shepero, Mahmoud, 1992-, et al.
(författare)
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Residential probabilistic load forecasting : A method using Gaussian process designed for electric load data
- 2018
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Ingår i: Applied Energy. - : Elsevier BV. - 0306-2619 .- 1872-9118. ; 218, s. 159-172
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Tidskriftsartikel (refereegranskat)abstract
- Probabilistic load forecasting (PLF) is of important value to grid operators, retail companies, demand response aggregators, customers, and electricity market bidders. Gaussian processes (GPs) appear to be one of the promising methods for providing probabilistic forecasts. In this paper, the log-normal process (LP) is newly introduced and compared to the conventional GP. The LP is especially designed for positive data like residential load forecasting—little regard was taken to address this issue previously. In this work, probabilisitic and deterministic error metrics were evaluated for the two methods. In addition, several kernels were compared. Each kernel encodes a different relationship between inputs. The results showed that the LP produced sharper forecasts compared with the conventional GP. Both methods produced comparable results to existing PLF methods in the literature. The LP could achieve as good mean absolute error (MAE), root mean square error (RMSE), prediction interval normalized average width (PINAW) and prediction interval coverage probability (PICP) as 2.4%, 4.5%, 13%, 82%, respectively evaluated on the normalized load data.
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