| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 4. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 5. |
- Barletta, V, et al.
(författare)
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Quantitative 7-Tesla Imaging of Cortical Myelin Changes in Early Multiple Sclerosis
- 2021
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 12, s. 714820-
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Tidskriftsartikel (refereegranskat)abstract
- Cortical demyelination occurs early in multiple sclerosis (MS) and relates to disease outcome. The brain cortex has endogenous propensity for remyelination as proven from histopathology study. In this study, we aimed at characterizing cortical microstructural abnormalities related to myelin content by applying a novel quantitative MRI technique in early MS. A combined myelin estimation (CME) cortical map was obtained from quantitative 7-Tesla (7T) T2* and T1 acquisitions in 25 patients with early MS and 19 healthy volunteers. Cortical lesions in MS patients were classified based on their myelin content by comparison with CME values in healthy controls as demyelinated, partially demyelinated, or non-demyelinated. At follow-up, we registered changes in cortical lesions as increased, decreased, or stable CME. Vertex-wise analysis compared cortical CME in the normal-appearing cortex in 25 MS patients vs. 19 healthy controls at baseline and investigated longitudinal changes at 1 year in 10 MS patients. Measurements from the neurite orientation dispersion and density imaging (NODDI) diffusion model were obtained to account for cortical neurite/dendrite loss at baseline and follow-up. Finally, CME maps were correlated with clinical metrics. CME was overall low in cortical lesions (p = 0.03) and several normal-appearing cortical areas (p < 0.05) in the absence of NODDI abnormalities. Individual cortical lesion analysis revealed, however, heterogeneous CME patterns from extensive to partial or absent demyelination. At follow-up, CME overall decreased in cortical lesions and non-lesioned cortex, with few areas showing an increase (p < 0.05). Cortical CME maps correlated with processing speed in several areas across the cortex. In conclusion, CME allows detection of cortical microstructural changes related to coexisting demyelination and remyelination since the early phases of MS, and shows to be more sensitive than NODDI and relates to cognitive performance.
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| 6. |
- Granberg, T, et al.
(författare)
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Corrigendum
- 2018
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 141:2, s. e14-
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Herranz, E, et al.
(författare)
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Profiles of cortical inflammation in multiple sclerosis by 11C-PBR28 MR-PET and 7 Tesla imaging
- 2020
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 26:12, s. 1497-1509
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation with microglia activation is thought to be closely related to cortical multiple sclerosis (MS) lesion pathogenesis. Objective: Using 11C-PBR28 and 7 Tesla (7T) imaging, we assessed in 9 relapsing–remitting multiple sclerosis (RRMS) and 10 secondary progressive multiple sclerosis (SPMS) patients the following: (1) microglia activation in lesioned and normal-appearing cortex, (2) cortical lesion inflammatory profiles, and (3) the relationship between neuroinflammation and cortical integrity. Methods: Mean 11C-PBR28 uptake was measured in focal cortical lesions, cortical areas with 7T quantitative T2* (q-T2*) abnormalities, and normal-appearing cortex. The relative difference in cortical 11C-PBR28 uptake between patients and 14 controls was used to classify cortical lesions as either active or inactive. Disease burden was investigated according to cortical lesion inflammatory profiles. The relation between q-T2* and 11C-PBR28 uptake along the cortex was assessed. Results: 11C-PBR28 uptake was abnormally high in cortical lesions in RRMS and SPMS; in SPMS, tracer uptake was significantly increased also in normal-appearing cortex. 11C-PBR28 uptake and q-T2* correlated positively in many cortical areas, negatively in some regions. Patients with high cortical lesion inflammation had worse clinical outcome and higher intracortical lesion burden than patients with low inflammation. Conclusion: 11C-PBR28 and 7T imaging reveal distinct profiles of cortical inflammation in MS, which are related to disease burden.
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| 13. |
- Jonsson, C. E., et al.
(författare)
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High-resolution diatom d18O records from two sub-Arctic high-altitude lakes in the Swedish Scandes
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Ingår i: Journal of Quaternary Science. - 0267-8179 .- 1099-1417.
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Tidskriftsartikel (refereegranskat)abstract
- Waters from high altitude alpine lakes are mainly recharged by meteoric water. Because of seasonal variations in precipitation and temperature, and relatively short hydraulic residence times, most high altitude lakes have lake water isotopic compositions (δ18Olake) that fluctuate due to seasonality in water balance processes. Input from snowmelt, in particular, has a significant role in determining lake water d18O. Here we compare two high resolution δ18Odiatom records from lake sediments in the Swedish Scandes with instrumental data from the last century obtained from nearby meteorological stations. The time period AD 1900 to AD 1990 is characterized by an increase in winter precipitation and high winter/summer precipitation ratios and this is recorded in δ18Odiatom as decreasing trends. Lowest δ18Odiatom values and highest amount of winter precipitation are found around AD 1990 when the winter North Atlantic Oscillation index was above +2. We conclude that for the last 150 years the main factor affecting the δ18Odiatom signal in these sub-Arctic high altitude lakes with short residence times has been changes in amount of winter precipitation and that δ18Odiatom derived from high altitude lakes in the Swedish Scandes can be used as a winter precipitation proxy.
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| 14. |
- Jonsson, C. E., et al.
(författare)
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Two diatom oxygen isotope records from Naimakka in northern Fennoscandia: implications for Holocene palaeohydrology and atmospheric circulation dynamics
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This study present past changes in lake water oxygen isotope composition (δ18Olakew) calculated from diatom oxygen isotope composition (δ18Odiatom) from two lake sediment records. The two sediment sequences (9500 and 2800 years) are from open-basin lakes, although with different hydrologies, and are located close to a meteorological station in Naimakka, Northern Fennoscandia. The isotope composition of lake waters was analysed to determine the modern regional hydrological setting. Our results show that changes in the isotope composition of precipitation (δ18Op) is the primary forcing mechanism decreasing or increasing the δ18Olakew values in both lakes. Changes in the isotope signals are interpreted as reflecting regional variations in atmospheric circulation and climatic seasonality. δ18Odiatom from Lake Keitjoru, covering the last 9500 years, shows a depletion trend of 1.3‰ from c. 8000 until around 1500 cal yr BP. This decrease is thought to be due to a long term decrease in the influence of a zonal airflow (strong westerlies, relatively high δ18Op) over Fennoscandia in favor of an increasing proportion of colder meridional airflow (weak westerlies, lower δ18Op) from the north. A synchronous shift to lower δ18O values was recorded in Lake Keitjoru and lake Oikojärvi around 700-600 cal yr BP (~AD 1250-1350), a time when European climate deteriorated into the “Little Ice Age”. We argue that a circulation pattern dominated by meridional airflow, with reduced westerlies over Northern Fennoscandia and high amounts of winter precipitation from southeast or north, replaced a zonal atmospheric circulation pattern at this time. The δ18Odiatom minima c. 400 and 50 cal yr BP (~AD 1550 and AD 1900) is likely also a response to shifts in circulation, which is also seen in lower summer temperatures at that time recorded in tree-rings and from pollen data. The fact that the same isotope shifts have been detected in δ18O records from hydrological different lakes lends support to our conclusion that these records reflect variations in atmospheric circulation pattern.
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