| 11. |
- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87 × 10(-9); odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53 × 10(-9); odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 12. |
- Hällström, Lina, et al.
(författare)
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Geochemical characterization of W, Cu and F skarn tailings at Yxsjöberg, Sweden
- 2018
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Ingår i: Journal of Geochemical Exploration. - : Elsevier. - 0375-6742 .- 1879-1689. ; 194, s. 266-279
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Tidskriftsartikel (refereegranskat)abstract
- Little attention has been paid to tailings from skarn ore deposits and their environmental impact, even though they can contain elevated concentrations of elements of potential concern together with sulfides and fluorite. Historical skarn tailings at Yxsjöberg, Sweden, containing e.g. Be, Bi, Cu, F, Sn, S, W, and Zn were geochemically characterized as a first step to evaluate the environmental impact and the potential to re-mine the tailings. The tailings were deposited between 1897 and 1963 in the Smaltjärnen Repository without dams or a complete cover, and have been in contact with the atmosphere for >30 years. Four vertical cores throughout the tailings were taken and divided into 134 subsamples, which were analyzed for total concentrations and paste pH. Selected samples from different depths were mineralogically characterized using optical microscopy, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), Raman vibrational spectroscopy, and X-ray diffraction (XRD). Minerals, hand-picked from drilled rock cores, were analyzed for the element content, and a modified Element to Mineral Conversion (EMC) that pinpoints the quantitative distribution of elements between the minerals in the tailings was carried out. The average concentrations of Be, Bi, Cu, Sn, Zn, W, F and S in the tailings were 284, 495, 946, 559, 301, and 960 ppm, and 1.9 and 1.2 wt%, respectively. The tailings has reached a late stage development due to pyrrhotite oxidation resulting in low pH (<4) in the uppermost tailings, and formations of secondary minerals such as gypsum, hydrous ferric oxides (HFO) and orthogonal calcite. Secondary pyrite and magnetite, formed from monoclinic pyrrhotite was detected, and different weathering rates of secondary pyrite, hexagonal and monoclinic pyrrhotite was indicated, with secondary pyrite as the most stable and monoclinic pyrrhotite as the least. The rare and easily-weathered mineral danalite (Fe4Be3(SiO4)3S) was found in the drilled rock cores and by XRD in the tailings. However, the mineral could not be found by optical microscopy or SEM-EDS. This suggests that the mineral has been weathered to a great extent, which poses a high risk of releasing elements of potential concern to the groundwater since danalite contains approximately 40% of the total Be and Zn concentrations in the tailings. Fluorine was mainly found in fluorite, Cu in chalcopyrite, and Bi in bismuthinite; which all showed signs of weathering in acidic condition in the uppermost part, subsequent with decreased concentrations, followed by accumulation peaks deeper down in the tailings correlated with Al. Tungsten was mainly found in scheelite; most grains were unweathered, but a few grains had altered rims or HFO on the mineral surfaces. Tin was mainly found in ferrohornblende, hedenbergite and grossular. Beryllium, Cu, F, and Zn has high potential to be released to the surrounding environment from the Smaltjärnen Repository, while W, Bi and Sn are relatively stable in the tailings. Most of the scheelite is intact and re-mining could, therefore, be a suitable remediation method that would both reduce the environmental impact and simultaneously support the supply of critical raw materials in the EU.
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| 13. |
- Hällström, Lina, et al.
(författare)
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Metal Release from Acidic and Near-Neutral pH-Conditions in Historical W, Cu and F Skarn Tailings at Yxsjöberg, Sweden
- 2018
-
Ingår i: 11th ICARD | IMWA | WISA MWD 2018 Conference. - 9780620806503 ; , s. 351-356
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Konferensbidrag (refereegranskat)abstract
- Weathering products stored in the pore water and/or as easily soluble salts in historical skarn tailings containing Be, Bi, Cu, W, and Zn, were released in water soluble fraction in the upper-most acidic tailings, at the visual oxidation front (1.5m), and/or below 2.5m (pH>7). Thus, there is a risk that these metals can pollute receiving waters by neutral mine drainage. Re-mining the tailings could be a suitable remediation method that would both reduce the environmental impact and simultaneously support the supply of metals.
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| 14. |
- Hällström, Lina, P.B
(författare)
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Geochemical Characterization of Historical W, Cu and F Skarn Tailings at Yxsjöberg, Sweden : With focus on scheelite weathering and tungsten (W) mobility
- 2018
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Little attention has been paid to tailings from skarn ore deposits and their environmental impact, even though they can contain elevated content of elements of potential concern. Historical skarn tailings from a former scheelite mine at Yxsjöberg, Sweden, containing e.g. Be, Bi, Cu, F, Sn, S, W, and Zn were geochemically characterized as a first step to evaluate the potential environmental impact and if re-mining of the tailings can be a remediation option. Beryllium, Bi, F, and W are considered as elements of potential concern, and are at the same time listed by the European Commission (2017) as critical raw materials. Scheelite is considered as a relatively stable mineral but most research has been focused on extraction processes. A few laboratory studies have shown weathering of scheelite by artificial groundwater, where the release of WO42-was hypothesized to be due to anion exchange by CO32-. Thus, the release of W from scheelite should be favorable in skarn tailings due to the presence of carbonates.The tailings at Yxsjöberg were deposited between 1897 and 1963 in the Smaltjärnen Repository without dams or a complete cover, and have been in contact with the atmosphere for more than 30 years. Four vertical cores (P2, P4, P5, and P7) throughout the tailings were taken and divided into 134 subsamples, and analyzed for their total chemical composition and paste pH. Selected samples from different depths were mineralogically characterized using optical microscopy, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), Raman vibrational spectroscopy, and X-ray diffraction (XRD). Minerals, hand-picked from drilled rock cores, were analyzed for the element content, and a modified Element to Mineral Conversion (EMC) in combination with a 7-step sequential extraction of the tailings was used to pinpoint the quantitative distribution of elements between the minerals in the tailings. Scheelite weathering and secondary sequestration of W was studied in detail in one representative core. The release of elements to groundwater in the tailings and downstream surface water was measured monthly during 2018 to especially examine the mobility of W.The average concentrations of Be, Bi, Cu, Sn, Zn, W, F and S in the tailings were 280, 490, 950, 560, 300, and 960 ppm, and 1.9 and 1.2 wt.%, respectively. The uppermost tailings have been exposed to the atmosphere for more 30 years, with intensive pyrrhotite oxidation and carbonate dissolution, resulting in low pH (<4) condition, release of elements, and subsequent formations of secondary minerals such as gypsum and hydrous ferric oxides (HFO). Two different deposition periods were identified in one vertical profile. The later period of deposition extended from the ground surface down to 3.5 m, and the older from 3.6 to 6 m. Both periods had unoxidized tailings in the bottom and oxidized sulfides, depletion of calcite and HFO formations upwards.Tungsten was primarily found in scheelite and the abundance was 0.1 wt.% in the tailings at Yxsjöberg. Accumulation peaks of W were found with depth in P2, P4 and P7. In the upper peak of P4, 30% of the total W was associated with secondary HFO. This indicates that weathering of scheelite and secondary capturing of W had occurred in the tailings. At present time, a peak of W in water soluble phases where coinciding with accumulated C in the solid phase at 2.5m depth. Carbonate ions were released when calcite was neutralizing the acid produced in the upper oxidized tailings and the released CO32-was transported downwards to conditions with pH >7. There, it mainly had precipitated as secondary calcite, but small parts are hypothesized to have exchanged WO42-on the surface of scheelite,releasing WO42-to the pore water. In the oxidized tailings of the older and deeper tailing,goethite was found as rims around scheelite grains. This is probably due to Fe ions attracted to the negative surface of scheelite. This is suggested to decrease further weathering of scheelite, and also to some extent decrease the release of WO42-to the groundwater from above lying layers through adsorption.The changes in geochemical conditions in the tailings have decreased the water quality in receiving waters of Smaltjärnens Repository with increased concentrations of Ca, F, Fe,Mn, and SO42-. pH was on average 6.3 in the groundwater in the tailings and 5.7 in the surface water 300 m downstream. EC was on average 2.6 mS/cm in the groundwater and 131 μS/cm in the surface water. Low concentrations of dissolved W was found in the groundwater (max: 20 μg/l) in the tailings and in the downstream surface water the W concentration (max: 0.2 μg/l) was 20 times larger than the reference sample. These results show that scheelite is releasing W to a limited degree to downstream waters and are therefore a potential resource to re-mine to support the supply of critical raw materials in the EU.Beryllium, F, and Zn were released to the downstream surface water from the Smaltjärnen Repository, and to a higher degree than W. The rare and easily-weathered mineral danalite (Fe4Be3(SiO4)3S) contained approximately 40% of the total Be and Zn concentrations in the tailings and is suggested to be the major source to the release of Be and Zn. Fluorine was mainly found in fluorite which showed signs of weathering in the acidic condition in the uppermost oxidized tailings, subsequent with decreased content in the tailings. The mobility of these elements will be further studied.
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| 15. |
- Hällström, Lina P.B., et al.
(författare)
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The geochemical behaviour of Be and F in historical mine tailings of Yxsjöberg, Sweden
- 2020
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Ingår i: Journal of Geochemical Exploration. - : Elsevier. - 0375-6742 .- 1879-1689. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- The speciation, mobility, transport, and fate of beryllium (Be) in the terrestrial environment is poorly studied even though it is considered to be one of the most hazardous elements in the periodic table. Historical tailings containing the unusual mineral danalite [Be3(Fe4.4Mn0.95Zn0.4)(SiO4)3.2S1.4] together with Fe-sulfides and fluorite has been stored open to the atmosphere for more than 50y. Environmental mineralogy, which combines geochemical and mineralogical techniques, was used to elucidate the weathering of danalite and fluorite. Danalite is unstable in oxic conditions due to the occurrence of Fe(II) and S-(II) in the crystal lattice and has oxidized at the same pace as pyrrhotite in the tailings. The acidic conditions generated from sulfide oxidation and the release of F from fluorite weathering have most likely enhanced Be mobility in the tailings. Secondary gypsum, hydrous ferric oxides and Al-oxyhydroxides are hypothesized to have played an important role regarding the mobility of Be in the tailings. The results indicate that Be released from danalite was first scavenged by these secondary minerals through co-precipitation. However, the dissolution of secondary gypsum due to changing geochemical conditions has also released Be to the groundwater. The groundwater at the shore of the tailings revealed the highest Be concentrations measured anywhere in the world (average: 4.5 mg/L) even though the water has a circumneutral pH. This extraordinary finding can be explained by high concentrations of F (73 mg/L), as F and Be have been shown to form strong complexes. The weathering of danalite and fluorite will continue for hundreds of years if remediation measures are not taken. Re-mining the tailings could be an appropriate remediation method.
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| 16. |
- Hällström, Lina, et al.
(författare)
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Scheelite weathering and tungsten (W) mobility in historical oxidic-sulfidic skarn tailings at Yxsjöberg, Sweden
- 2020
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Ingår i: Environmental Science and Pollution Research. - : Springer. - 0944-1344 .- 1614-7499. ; 27:6, s. 6180-6192
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Tidskriftsartikel (refereegranskat)abstract
- More knowledge of the geochemical behavior of tungsten (W) and associated contamination risks is needed. Therefore, weathering of scheelite (CaWO4) and secondary sequestration and transport of W to groundwater in historical skarn tailings and surface water downstream of the tailings were studied. The tailings contained 920 mg/kg W, primarily in scheelite. Mineralogical and geochemical analyses were combined to elucidate the geochemical behavior of W in the tailings, and water samples were taken monthly during 2018 to monitor its mobility. In the tailings, a large peak of W was found at 1.5 m depth. There, 30 wt%. of W was present in easily reducible phases, indicating former scheelite weathering. Currently, W is being released from scheelite to water-soluble phases at 2.5 m depth. The release of WO42− is hypothetically attributed to anion exchange with CO32− released from calcite neutralizing acid produced from pyrrhotite oxidation in the upper tailings and transported downwards to pH conditions > 7. Higher concentrations of dissolved W were found in the groundwater and particulate W in downstream surface water than in reference water, but they were lower than current contamination thresholds. Tungsten showed correlations with hydrous ferric oxides (HFO) in both the tailings and surface water.
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| 17. |
- Hällström, Lina
(författare)
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Source, mobility and fate of critical Be, Bi, F and W from historical sulfidic-oxidic skarn tailings : Re-mining as remediation method?
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a potential risk that geochemical cycles of several critical metals will be affected in the pristine environment, when mining of these metals increases to meet the demand in green technology. The identification of critical metals is based on the economic importance and vulnerability to supply restrictions. In the past, naturally low concentrations in the environment, and instrumental analysis with higher detection limits, has limited research regarding several of these critical metals. However, to understand their geochemical behavior and potential environmental impact are of high importance to ensure a responsible development of mine waste- and water management. Skarn ores can contain high amounts of Fe-sulfides, carbonates and fluorite, together with enriched concentrations of critical metals such as Be, Bi and W. Nevertheless, little attention has been paid to mine drainage from skarn tailings and their environmental impact, compared to tailings from sulfidic deposits. At Yxsjö mine site, Sweden, skarn tailings enriched in the major elements C, F, S (1.0, 1.9 and 1.2 wt.%.) and Be, Bi, and W (average 280, 500 and 960 ppm, respectively) were deposited in Smaltjärnen repository (1918-1963). The tailings were stored in ambient conditions until 1993 when the tailings were covered by sewage sludge. In-between 1969-1989, tailings were discharged into Morkulltjärnen repository, which was covered with sewage sludge and partly water saturated directly after closure. This thesis focuses on the Smaltjärnen tailings. The element distribution in the tailings were identified by combining 1) total concentrations of nine targeted minerals from rock drilled cores, 2) total concentrations of 99 samples from four intact tailings cores, and 3) environmental mineralogy (EM) conducted on one of the cores. The environmental mineralogy included paste-pH, sequential extractions, optical microscopy, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), Raman vibrational spectroscopy and X-ray diffraction (XRD). Environmental mineralogy was also used to reveal geochemical processes affecting the mobility of elements in the tailings. Monthly water samples (May-October, 2018) were taken in three groundwater wells in the tailings, and at five surface water locations downstream the tailings. At three surface water locations, the diatom taxonomy response to the water quality was used to evaluate the impact on ecosystems. The quality of the mine drainage was compared to surface water downstream Morkulltjärnens repository and to a reference point. The overall results were used to evaluate the need for remediation, and particularly, the possibility to use re-mining as remediation method. The Smaltjärnen tailings contained 88 wt.%. of Ca-rich silicates accompanied by minerals such as calcite [CaCO3], fluorite [CaF2], monoclinic and hexagonal pyrrhotite [Fe1-xS)], danalite [Be3(Fe4.4Mn0.95Zn0.4)(SiO4)3.2S1.4], scheelite [CaWO4] and bismuthinite [Bi3S2] (average 5.7, 3.6, 2.4, 0.3, 0.1 wt.%. and 0.1 wt.%., respectively). Both pyrrhotite and danalite had oxidized in the upper parts of the tailings down to 2.5m depth, and calcite had partly neutralized the acid produced resulting in a pH decrease from 8 to 4 in the upper parts of the tailings. Weathering of danalite was intensified by the more acidic conditions (pH<6), in which Be hydrolyzes. The lowered pH enabled dissolution of fluorite, resulting in severely high concentrations of F in the groundwater (average 73 mg/L) and surface water (average 1.6 mg/L). In the uppermost tailings, secondary gypsum [CaSO4], Al-complexes and hydrous ferric oxides (HFO) had formed. The geochemical behavior of Be was complex in the tailings and in surface water downstream the tailings. According to the sequential extraction, Be released from danalite in the upper most tailings were present in water soluble phases, as exchangeable phases and had co-precipitated with Al- and Fe-oxyhydroxides. A strong correlation between Be, Ca and S in water soluble phases and in the surface water downstream the tailings indicated that Be partly substituted for Ca in secondary gypsum. In two groundwater wells, secondary precipitates of a white sludge containing Be, Al, F and Zn were found, indicating that Be was partly removed from the groundwater by Al-complexes. In the third groundwater well, the globally highest dissolved concentrations of Be were measured (average 4.5 mg/L), and in the surface water the concentrations (average 41 µg/L) were well above thresholds values for aquatic organisms (1 µg/L). In these pH-conditions (average 5.7-6.5) and oxygenated waters, Be is expected to precipitate as Be(OH)2 if complexing ligands are absent. A strong correlation between dissolved Be and F was found in the surface water, indicating that Be-fluorocomplexes had formed. Bismuth and W have previously been considered as relatively immobile elements. However, the results showed that both Bi and W had partly been mobilized from their primary minerals (bismuthinite and scheelite) in the tailings. Weathered bismuthinite and scheelite grains with rims of goethite and water soluble phases of Bi and W were found in the deeper tailings with pH>7. The release of WO42- was hypothetically attributed to anion exchange with CO32- on surfaces of scheelite. Because, at the same depth where W was mobilized, solid C was accumulated and secondary orthogonal calcite was frequently detected with Raman spectroscopy. Bismuth was scavenged in the tailings by exchangeable phases and co-precipitation with HFO in the upper-most tailings. In the groundwater, Bi was just above the detection limit in all groundwater wells, while W was found in elevated concentrations. In the surface water, Bi and W were transported in the particulate phase together with Fe, and settled in the sediments a few 100 meters from the tailings outlet. Surface water downstream Morkulltjärnen had a near-neutral pH (average 6.6) and of all elements analyzed, only dissolved W (average 1.1 µg/L) were high compared to threshold values (0.8 µg/L) and the reference sample. Dissolved Be, Ca, F and S from Smaltjärnen, and dissolved W from Morkulltjärnen were found in elevated concentrations more than 2 km from the mine site. Along this distance, metal tolerant diatom species (Achnanthidium minutissimum group II and Brachysira neoexilis, respectively) were dominant (>50%), indicating a negative impact on ecosystems. The mine drainage from Smaltjärnen had a larger negative impact on the diatom taxonomy with higher abundance of metal tolerant species, lower richness and evenness, more than 1% of deformed valves and the taxonomy was affected by the lower pH, compared to diatoms downstream Morkulltjärnen repository. In conclusion, pyrrhotite oxidation was the direct or indirect cause of Be, Bi, F and W mobilization in the Smaltjärnen tailings, resulting in low quality mine drainage. The oxidation rate decrease with time, but weathering of the Smaltjärnen tailings is expected to be ongoing for hundreds of years since only a small part had weathered during the 50-100 years of storage. The low water quality and negative impact on diatoms, stress the need for remediation. Low concentrations of Be, Bi, Ca, F, Fe and S, accompanied by a near-neutral pH (average pH 6.6) downstream Morkulltjärnen, suggested that cover and water saturation could inhibit sulfide and danalite oxidation, and indirectly prevent fluorite weathering. However, high concentrations of dissolved W downstream Morkulltjärnen displayed that cover and water saturation can increase the mobility of W in the Smaltjärnen tailings, which needs to be taken into consideration. This thesis shows the importance of understanding the complex mineral and element matrix in skarn tailings before choosing remediation technique. Re-mining could be a beneficial remediation method since most W were found in intact scheelite grains. However, more research regarding the mineral processing and metallurgy is needed to ensure a sustainable extraction technique that separates sulfides, carbonates, danalite and fluorite, and deposits them in a proper way.
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| 18. |
- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 19. |
- Kelsoe, John, et al.
(författare)
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Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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| 20. |
- Lindahl, Bertil, et al.
(författare)
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An algorithm for rule-in and rule-out of acute myocardial infarction using a novel troponin I assay
- 2017
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:2, s. 125-131
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Tidskriftsartikel (refereegranskat)abstract
- Objective To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay. Methods The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers. Results In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts. Conclusions This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively.
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