| 1. |
- Bruzelius, Maria, et al.
(författare)
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F11 is associated with recurrent VTE in women A prospective cohort study
- 2016
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Ingår i: Thrombosis and Haemostasis. - : Schattauer Gmbh. - 0340-6245 .- 2567-689X. ; 115:2, s. 406-414
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Tidskriftsartikel (refereegranskat)abstract
- Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002-2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) between groups. A total of 101 recurrent events occurred during a mean follow-up time of five years. The overall recurrence rate was 20 per 1,000 person-years (95 % CI; 16-24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95 % CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95 % CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction.
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| 2. |
- Bruzelius, Maria, et al.
(författare)
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Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism
- 2014
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 134:2, s. 426-432
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case-control study (n = 2753) from Sweden. Materials and Methods: 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. Results: Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181). Conclusions: It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.
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| 3. |
- Bruzelius, Maria, et al.
(författare)
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PDGFB, a new candidate plasma biomarker for venous thromboembolism : results from the VEREMA affinity proteomics study
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:23, s. E59-E66
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Tidskriftsartikel (refereegranskat)abstract
- There is a clear clinical need for high-specificity plasma biomarkers for predicting risk of venous thromboembolism (VTE), but thus far, such markers have remained elusive. Utilizing affinity reagents from the Human Protein Atlas project and multiplexed immuoassays, we extensively analyzed plasma samples from 2 individual studies to identify candidate protein markers associated with VTE risk. We screened plasma samples from 88 VTE cases and 85 matched controls, collected as part of the Swedish Venous Thromboembolism Biomarker Study, using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins. We identified significant associations between VTE occurrence and plasma levels of human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1), von Willebrand factor (VWF), glutathione peroxidase 3 (GPX3), and platelet-derived growth factor beta (PDGFB). For replication, we profiled plasma samples of 580 cases and 589 controls from the French FARIVE study. These results confirmed the association of VWF and PDGFB with VTE after correction for multiple testing, whereas only weak trends were observed for HIVEP1 and GPX3. Although plasma levels of VWF and PDGFB correlated modestly (rho similar to 0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF P < .001; PDGFB P = .002). PDGF. was verified as the target of the capture antibody by immunocapture mass spectrometry and sandwich enzyme-linked immunosorbent assay. In conclusion, we demonstrate that high-throughput affinity plasma proteomic profiling is a valuable research strategy to identify potential candidate biomarkers for thrombosis-related disorders, and our study suggests a novel association of PDGFB plasma levels with VTE.
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| 4. |
- Majeed, Ammar, et al.
(författare)
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Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates : a cohort study
- 2017
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Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 130:15, s. 1706-1712
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Tidskriftsartikel (refereegranskat)abstract
- There is uncertainty regarding the effectiveness and occurrence of thromboembolic events in patients treated with prothrombin complex concentrates (PCCs) for the management of major bleeding events (MBEs) onrivaroxabanor apixaban. We investigated the effectiveness of PCCs given for the management of MBEs in patients on rivaroxaban or apixaban. Between 1 January 2014 and 1 October 2016, we prospectively included patients on rivaroxaban or apixaban treated with PCCs for the management of MBEs. The effectiveness of PCCs was assessed by using the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria for the assessment of the effectiveness of major bleeding management. The safety outcomes were thromboembolic events and all-cause mortality with in 30 days after treatmentwith PCCs. Atotal of 84 patients received PCCs for the reversal of rivaroxaban or apixaban due to a MBE. PCCs were given at amedian (interquartile range) dose of 2000 IU (1500-2000 IU). Intracranial hemorrhage (ICH) was themost common site of bleeding requiring reversal (n = 5 59; 70.2%), followed by gastrointestinal bleeding in 13 (15.5%) patients. Management with PCCs was assessed as effective in 58 (69.1%) patients and ineffective in 26 (30.9%) patients. Most patients with ineffective hemostasis with PCCs had ICH (n 5 16; 61.5%). Two patients developed an ischemic stroke, occurring 5 and 10 days after treatment with PCC. Twenty seven (32%) patients died within 30 days after a MBE. The administration of PCCs for the management of MBEs associated with rivaroxaban or apixaban is effective inmost cases and is associated with a low risk of thromboembolism. Our findings are limited by the absence of a control group in the study.
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| 5. |
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| 6. |
- Bergek, Anna, 1973-, et al.
(författare)
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Are patents with multiple inventors from different countries a good indicator of international R&D collaboration? The case of ABB
- 2010
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Ingår i: Research Policy. - : Elsevier BV. - 0048-7333 .- 1873-7625. ; 39, s. 1321-1334
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Tidskriftsartikel (refereegranskat)abstract
- Based on the critical case of ABB, this paper questions the relevance of using patents with multiple inventors from different countries (“cross-country patents”) as an indicator of international R&D collaboration. The study shows that less than half of ABB’s cross-country patents are the result of international R&D collaboration as described by one of the more inclusive definitions found in previous literature. Only a third of the patents are the result of joint R&D activities between different MNC subsidiaries or firms. We also discuss the implications of our study for the assignment of patents to countries based on inventor addresses.
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| 7. |
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| 8. |
- Bruzelius, Fredrik, et al.
(författare)
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Test report
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is the document summarising the testing experience and knowledge gained from the physical testing activities within the eVALUE project. The document contains brief introductions to the testing scenarios as well as short summaries of conclusions. Appended to this document are the testing reports that have been compiled during the different test sessions. Physical testing at test tracks all across Europe has been the main input in the development of scenarios and test procedures. This document describes the development tests that have been performed during 2010, based on a first draft set of testing protocols. The experience from the performed tests has been used as an important input to the revision of the testing protocols, i.e. the formal documents that describe how a test should be performed and evaluated. These protocols are documented in the separate Deliverable 3.2.
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| 9. |
- Bruzelius, Maria
(författare)
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Exploration of novel mechanisms and biomarkers for venous thromboembolism : a genetics and proteomics study
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Venous thromboembolism (VTE) contributes to a large health burden and incidence increases exponentially with age. ~25% patients will experience a recurrent event and there is a 2-fold risk for death in the following years. Risk prediction remains a challenge. Aims to: Investigate a presumed overlap between cardiovascular disease and VTE. Expand current knowledge of established pathways in VTE risk by combining clinical and genetic epidemiology. Apply affinity proteomics to identify novel plasma susceptibility biomarkers. Methods and results: 39 single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) and 18 risk VTE-SNPs from candidate gene approach studies or genome-wide association studies (GWAS) were identified from a literature search. The SNPs were genotyped in 2,835 women from the ThromboEmbolism Hormone study (TEHS), a Swedish nationwide case-control study in women (2002-2009). Association was assessed with logistic regression. Clinical and genetic predictors that contributed significantly to the fit of the logistic regression model were included in the prediction models. The genetic predictors that contributed to first VTE were assessed in a cohort of 1010 women with VTE from TEHS, followed up until a recurrence, death or November 2011 (TEHS follow-up). The SNP r579459 in the ABO locus was the only CAD-SNP that was significant associated with VTE (OR 1.57 (95% CI: 1.39-1.78, p= 6.4 10-13)). Seven VTE risk-SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446) with 4 SNP-SNP interactions contributed to the genetic risk score for VTE with an AUC of 0.66 (95% CI: 0.64-0.68). After adding clinical risk factors the AUC attained 0.84 (95% CI: 0.82-0.85). The goodness of fit of the genetic and combined scores improved when significant SNP-SNP interaction terms were included. In TEHS follow-up study, the overall recurrence rate was 20 per 1000 person-years (95% CI; 16-24). Carriers of the risk alleles of F5 rs6025 (FVL) (HR=1.7 (95% CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95% CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at 5 years follow-up. Plasma samples from 88 VTE cases and 85 controls, part of the Venous thromboembolism Biomarker Study (VEBIOS), were screened against 408 candidate proteins targeted by 755 antibodies using multiplex bead arrays. Proteins that significantly associated with VTE after Bonferroni correction were tested for replication in plasma samples of 580 cases and 589 controls from the FARIVE study. In VEBIOS, plasma levels of four proteins, HIVEP1, VWF, GPX3 and PDGFB were significantly associated with VTE after Bonferroni correction. VWF and PDGFB successfully replicated in FARIVE with increased plasma levels in VTE cases compared to controls as initially observed in VEBIOS. Conclusion: ABO locus was the only shared genetic risk factor between CVD and VTE. A limited set of genetic predictors improved prediction of incident VTE in women at high risk. Our data indicated that interactions among SNPs increase the goodness of fit when predicting VTE. A combination of genotypes i.e. F11 rs2289252 and FVL, may be of potential clinical relevance for risk prediction for recurrence. Affinity plasma proteomics proved to be a valuable research strategy to discover novel biomarkers
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| 10. |
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| 11. |
- Canals, Isaac, et al.
(författare)
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Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
- 2023
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Ingår i: Brain Communications. - 2632-1297. ; 5:3, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is the second most prevalent type of early-onset dementia and up to 40% of cases are familial forms. One of the genes mutated in patients is CHMP2B, which encodes a protein found in a complex important for maturation of late endosomes, an essential process for recycling membrane proteins through the endolysosomal system. Here, we have generated a CHMP2B-mutated human embryonic stem cell line using genome editing with the purpose to create a human in vitro FTD disease model. To date, most studies have focused on neuronal alterations; however, we present a new co-culture system in which neurons and astrocytes are independently generated from human embryonic stem cells and combined in co-cultures. With this approach, we have identified alterations in the endolysosomal system of FTD astrocytes, a higher capacity of astrocytes to uptake and respond to glutamate, and a neuronal network hyperactivity as well as excessive synchronization. Overall, our data indicates that astrocyte alterations precede neuronal impairments and could potentially trigger neuronal network changes, indicating the important and specific role of astrocytes in disease development.
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| 12. |
- Drouin-Ouellet, Janelle, et al.
(författare)
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Age-related pathological impairments in directly reprogrammed dopaminergic neurons derived from patients with idiopathic Parkinson's disease
- 2022
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Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 17:10, s. 2203-2219
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Tidskriftsartikel (refereegranskat)abstract
- We have developed an efficient approach to generate functional induced dopaminergic (DA) neurons from adult human dermal fibroblasts. When performing DA neuronal conversion of patient fibroblasts with idiopathic Parkinson's disease (PD), we could specifically detect disease-relevant pathology in these cells. We show that the patient-derived neurons maintain age-related properties of the donor and exhibit lower basal chaperone-mediated autophagy compared with healthy donors. Furthermore, stress-induced autophagy resulted in an age-dependent accumulation of macroautophagic structures. Finally, we show that these impairments in patient-derived DA neurons leads to an accumulation of phosphorylated alpha-synuclein, the classical hallmark of PD pathology. This pathological phenotype is absent in neurons generated from induced pluripotent stem cells from the same patients. Taken together, our results show that direct neural reprogramming can be used for obtaining patient-derived DA neurons, which uniquely function as a cellular model to study age-related pathology relevant to idiopathic PD.
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| 13. |
- Florén, Britta, et al.
(författare)
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Förstudie: Smart och klimatmedveten matbutik för morgondagens konsumenter och samhälle
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Vid sidan om transporter och bostäder så står maten för en av de stora klimatutmaningarna nu och framöver. Matens del av den totala konsumtionsdrivna klimatpåverkan i Sverige är idag cirka 25 %, ca 2 ton CO2-e per person och år. Genom att underlätta för konsumenter att välja mer klimatsmarta val vid livsmedelsinköp finns en möjlighet att minska klimatpåverkan från livsmedel. I ett nudgingförsök på mat.se sänkte medverkande kunder sin klimatpåverkan från livsmedel med 7 procent baserat på genomsnittliga kg CO2-e per order. Under motsvarande period minskade icke-deltagande konsumenter sitt klimatavtryck med 3 procent med samma beräkningsmetod. Förstudien har undersökt hur information om klimatpåverkan hos olika livsmedel tillsammans med tillgängliggörandet av klimatsmartare alternativ (nudging) kan förändra köpbeteendet hos konsumenten. Målet har varit att minska klimatpåverkan i staden. Förstudien har fokuserat på metoder och parametrar viktiga för att locka fler att medvetet eller omedvetet handla mer miljö-/klimat-smartare mat. Livskraftiga städer som uppmuntrar till hållbara livsstilar kräver innovativa lösningar som underlättar för konsumenten att välja rätt. Projektupplägget har bestått av en kartläggning av nuvarande situation, nudgingförsök samt projektworkshops. Kartläggningen genomfördes för att avgöra vilka produkter som är av specifikt intresse att tillgängliggöra klimatsmartare alternativ. RISE klimatdatabas för livsmedel har varit central i denna del för att identifiera vilka beslutsval som har kapacitet att ge en betydande klimatnytta. Nudgingförsöket har byggts upp i en två-stegs nudgingmodell där konsumenterna först har aktivt fått välja att medverka i projektet (steg 1). För de som väljer att förbinda sig till detta har klimatsmartare alternativ lyfts upp till det först visade alternativet vid vissa specifika sökord (steg 2). Projektdeltagare: - Mat.se, en innovativ aktör inom e-handel som vill utveckla lösningar för en minskad klimatpåverkan från livsmedelskonsumtion.- Göteborg Stad deltog som representant för medborgaren och staden, - Handelshögskolan (GU) med forskningsexpertis inom nudging. - RISE, experter inom livsmedels klimatpåverkan och beteendevetenskap.
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| 14. |
- Grosso, Giorgia, et al.
(författare)
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The Complex Relationship between C4b-Binding Protein, Warfarin, and Antiphospholipid Antibodies
- 2021
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 121:10, s. 1299-1309
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Tidskriftsartikel (refereegranskat)abstract
- Background Low levels of total C4b-binding protein (C4BPt), a circulating inhibitor of the classical/lectin complement pathways, were observed in patients with antiphospholipid antibodies (aPLs) and during warfarin treatment. Objectives To investigate the associations between aPL and C4BPt in patients with persistently positive (++) aPL, with/without clinical manifestations and systemic lupus erythematosus (SLE), and in controls. Furthermore, we explored the impact of anticoagulation on C4BPt and in relation to complement activation. Methods In a cross-sectional design we investigated defined subgroups: primary (p) antiphospholipid syndrome (APS, N =67), aPL++ individuals without clinical manifestations (aPL carriers, N =15), SLE-aPL++ ( N =118, among them, secondary [s] APS, N =56), aPL negative (-) SLE (SLE-aPL-, N =291), and 322 controls. Clinical characteristics, including treatment, were tabulated. C4BPt was determined with a magnetic bead method. Complement proteins (C1q, C2, C3, C4, C3a, C3dg, sC5b-9, factor I [FI]) were measured. A mediation analysis was performed to decompose the total effect of aPL++ on C4BPt into the direct and indirect effects of aPL++ through warfarin. Results Overall, C4BPt is 20% decreased in aPL++ patients, regardless of SLE, APS, clinical manifestations, and aPL profile. C4BPt levels associate positively with complement proteins C1q, C2, C3, and C4, and negatively with complement activation product C3dg. In the SLE group, warfarin treatment contributes to approximately half of the C4BPt reduction (9%) Conclusion Both aPLs and warfarin are associated with C4BPt reduction. Complement activation in aPL++ patients may partly be explained by impaired inhibition through depressed C4BPt levels. Further studies are needed to understand the clinical implications.
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| 15. |
- Hjort, Mattias, 1972-, et al.
(författare)
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Jämförelse av vinter och sommardäck på barmark sommartid : tester, riskanalys och djupstudier
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Allt fler bilister har ersatt sina dubbade vinterdäck med dubbfria. Eftersom det inte är olagligt att köra med odubbade vinterdäck på sommaren väljer ett stort antal förare att låta vinterdäcken sitta på även sommartid. Syftet med denna studie har varit att undersöka skillnad i väggrepp mellan vinter- och sommardäck sommartid, samt att uppskatta tänkbara trafiksäkerhetseffekter av att använda vinterdäck sommartid. En fältstudie genomfördes där väggrepp mättes på torr och våt asfalt med olika typer av däck. Resultaten visade att vinterdäcken (odubbade av Nordisk typ) i genomsnitt resulterade i 15–20 procent längre bromssträckor jämfört med sommardäcken. Skaderiskanalyser genomfördes för tre olika typer av trafikolyckor: bakifrånkollision, frontalkollision och påkörning av fotgängare. Studien visade på ökningar av skaderisken vid användning av vinterdäck istället för sommardäck för alla tre olyckstyperna. Vid låga kollisionshastigheter är den absoluta riskökningen liten kanske bara ett fåtal procent, medan den relativa ökningen kan vara stor, ibland upp till en fördubbling av risken. Djupstudier av dödsolyckor sommartid indikerade en riskökning på 3 procent vid användning av vinterdäck sommartid jämfört med sommardäck. Detta resultat är dock inte statistiskt signifikant.
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| 16. |
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| 17. |
- Jacobson, Jan, et al.
(författare)
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Final testing protocols
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is the final document summarizing the inspection and testing protocols of the eVALUE project. It describes principles, inspection protocols and testing protocols for performance testing of ICT-based safety systems. The inspection protocols (published earlier in D2.2) and the testing protocols introduced in D3.1 are replaced by the ones in D3.2. The older versions are obsolete and should be disregarded. The inspection protocols cover the definition of the test vehicle, HMI aspects, environmental conditions, and functional safety. The inspection protocols are used to prepare for the physical tests as well as evaluating the performance of the vehicle. The testing protocols address longitudinal, lateral, and stability-oriented traffic scenarios. The longitudinal scenarios include a pedestrian crossing the road in front of the vehicle, or the situation where a driver approaches a stationary queue of cars. Involuntarily lane departures and cars in the blind spot during a lane change are situations covered by the lateral scenarios. Exiting a highway, avoiding an obstacle, and braking on a partially ice-covered road surface are examples of traffic scenarios related to stability.
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| 18. |
- Kihlberg, Kristina, et al.
(författare)
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Treatment outcomes in persons with severe haemophilia B in the Nordic region : The B-NORD study
- 2021
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 27:3, s. 366-374
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Data on outcome in persons with haemophilia B (PwHB) are limited and mainly extrapolated from studies of haemophilia A (HA). Aim: To characterize treatment outcomes in persons with severe HB in the Nordic region, with a focus on joint health, compared with matched controls with HA. Methods: PwHB attending haemophilia centres in Denmark, Finland, Norway and Sweden were enrolled and matched with controls with HA. Joint assessment using Haemophilia Joint Health Score (HJHS) and ultrasound according to Haemophilia Early Arthropathy Detection protocol (HEAD-US) was conducted. Adherence was evaluated using the Validated Haemophilia Regimen Treatment Adherence Scale (VERITAS). Results: Seventy-nine males with HB, with median age of 30 years (range 1–75), were enrolled. Eleven patients (14%) had a history of or current inhibitor. Twenty-nine PwHB (37%) reported joint bleeds during the prior year, and 35% had previously undergone joint surgery. Ninety-five per cent were on prophylaxis, and 70% used recombinant concentrates, with a median factor consumption of 3,900 IU/kg/year for standard half-life products. Only two patients had a VERITAS score corresponding to ‘non-adherence'. Joint health, assessed with HJHS, showed a significant lower score among PwHB compared with HA controls, explained by a difference in the 18–49 age group, without observed differences in older or younger subgroups. The HEAD-US scores were overall low. Conclusion: The Nordic cohort of PwHB is well treated by prophylaxis, but the goal of zero bleeds for all is not reached. Our findings suggest that patients with severe HB suffer from a milder arthropathy than patients with severe HA.
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| 19. |
- Måseide, Ragnhild J., et al.
(författare)
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Haemophilia early arthropathy detection with ultrasound and haemophilia joint health score in the moderate haemophilia (MoHem) study
- 2021
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 27:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Detection of early arthropathy is crucial for the management of haemophilia, but data on moderate haemophilia are limited. Therefore, we evaluated joint health and treatment modalities in Nordic patients with moderate haemophilia A (MHA) and B (MHB). Aim: To explore and compare the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) and Haemophilia Joint Health Score (HJHS) to detect early arthropathy in moderate haemophilia. Methods: A cross-sectional, multicentre study covering Nordic patients with MHA and MHB. Arthropathy was evaluated by HEAD-US and HJHS 2.1. Results: We assessed 693 joints in 118 patients. HEAD-US scores (medians [interquartile ranges]) were as follows: elbows 0 points (0–0), knees 0 (0–0) and ankles 0 (0–1). Respectively, by HJHS: elbows 0 (0–1), knees 0 (0–1) and ankles 0 (0–1). Cartilage (14%) and bone (13%) were most commonly affected by HEAD-US. Frequent HJHS findings were crepitus on motion in knees (39%), and loss of flexion (23%) and extension (13%) in ankles. HEAD-US correlated strongly with HJHS (elbows r =.70, knees r =.60 and ankles r =.65), but 24% had discordant scores. Joints with HJHS zero points, 5% captured HEAD-US ≥1 point. Moreover, 26% had HJHS findings without HEAD-US pathology. Notably, 31% of knees had crepitus on motion and normal HEAD-US. Conclusion: Overall, the joints attained low scores implying good joint health. HEAD-US correlated strongly with HJHS. In 5%, HEAD-US detected subclinical pathology. Crepitus on motion was frequently reported despite normal HEAD-US, thus not necessarily reflecting arthropathy. HEAD-US therefore improves the joint assessment in moderate haemophilia.
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| 20. |
- Måseide, Ragnhild J., et al.
(författare)
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Health-related quality of life and physical activity in Nordic patients with moderate haemophilia A and B (the MoHem study)
- 2024
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Ingår i: Haemophilia. - 1351-8216. ; 30:1, s. 98-105
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The impact of moderate haemophilia on health-related quality of life (HRQoL) and physical activity (PA) is not well known. In previous studies, persons with factor VIII/factor IX activity (FVIII/FIX:C) below 3 IU/dL were associated with a more severe bleeding phenotype than predicted. Aim: To explore HRQoL and PA in patients with moderate haemophilia A (MHA) and B (MHB). Methods: A cross-sectional, multicentre study covering patients with MHA and MHB in Sweden, Finland, and Norway. HRQoL was assessed with the EuroQoL 5-Dimensions (EQ-5D) form and PA with the International Physical Activity Questionnaire among participants aged ≥15 years. Results: We report on 104 patients aged 15–84 years from the MoHem study. Overall, EQ-5D utility was.85 (median) (Q1–Q3 0.73–1.0) with corresponding visual analogue scale (VAS) 80 (70–90), which were similar regardless of treatment modality, FVIII/FIX:C, and MHA or MHB. Pain and mobility were most frequently affected dimensions. Utility (r = -.54), VAS (r = -.42), and PA (r = -.32) correlated negatively with arthropathy (HJHS). Only patients aged 41–50 years displayed lower utility (p =.02) and VAS (p <.01) than the Norwegian population norm. Patients on prophylaxis aged 35–54 years reported higher PA than those treated on-demand (p =.01). Conclusion: Haemophilic arthropathy had negative impact on HRQoL and PA in Nordic patients with moderate haemophilia. Middle-aged patients captured lower utility and VAS than observed in the general population. Tailored prophylaxis and improved joint health may influence positively on HRQoL and PA also in moderate haemophilia.
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| 21. |
- Måseide, Ragnhild J., et al.
(författare)
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Joint health and treatment modalities in Nordic patients with moderate haemophilia A and B – The MoHem study
- 2020
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 26:5, s. 891-897
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The prevalence of arthropathy in moderate haemophilia A (MHA) and B (MHB) is not well known. Aim: We evaluated joint health in Nordic patients in relation to their treatment modality. Methods: A cross-sectional, multicentre study covering MHA and MHB in Sweden, Finland and Norway. Arthropathy was evaluated by ultrasound (HEAD-US) and Haemophilia Joint Health Score (HJHS). Results: We report on 145 patients: median age 28 years (IQR 13-52) and 61% MHA. Baseline factor VIII/factor IX activity (FVIII/FIX:C) was 2 IU/dL (median) (IQR 2-4): lower for MHB (2 IU/dL, IQR 1-2) than MHA (3 IU/dL, IQR 2-4) (P <.01). Eighty-five per cent of MHA and 73% MHB had a history of haemarthrosis (P =.07). Age at first joint bleed was lower for MHA (5 years [median], IQR 3-7) than MHB (7 years, IQR 5-12) (P =.01). Thirty-eight per cent received prophylaxis, started at median 10 years of age (IQR 4-24). Median joint bleeds and serious other bleeds during the last 12 months were both zero (IQR 0-1). Total HEAD-US captured 0/48 points (median) (IQR 0-2) and HJHS 4/120 points (IQR 1-10) with strong correlation between them (r =.72). FVIII/FIX:C ≤ 3 IU/dL was associated with higher HJHS (P =.04). Fifteen per cent had undergone orthopaedic surgery. Conclusion: The current joint health in Nordic moderate haemophilia patients was rather good, but a subgroup had severe arthropathy. FVIII/FIX:C ≤ 3 IU/dL and MHA were associated with a more severe bleeding phenotype. We suggest primary prophylaxis to all patients with FVIII/FIX:C ≤ 3 IU/dL.
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| 22. |
- Nolbrant, Sara, et al.
(författare)
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Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons
- 2020
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Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 15:4, s. 869-882
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Tidskriftsartikel (refereegranskat)abstract
- Human glial progenitor cells (hGPCs) are promising cellular substrates to explore for the in situ production of new neurons for brain repair. Proof of concept for direct neuronal reprogramming of glial progenitors has been obtained in mouse models in vivo, but conversion using human cells has not yet been demonstrated. Such studies have been difficult to perform since hGPCs are born late during human fetal development, with limited accessibility for in vitro culture. In this study, we show proof of concept of hGPC conversion using fetal cells and also establish a renewable and reproducible stem cell-based hGPC system for direct neural conversion in vitro. Using this system, we have identified optimal combinations of fate determinants for the efficient dopaminergic (DA) conversion of hGPCs, thereby yielding a therapeutically relevant cell type that selectively degenerates in Parkinson's disease. The induced DA neurons show a progressive, subtype-specific phenotypic maturation and acquire functional electrophysiological properties indicative of DA phenotype.
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| 23. |
- Razzaq, M., et al.
(författare)
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Explainable Artificial Neural Network for Recurrent Venous Thromboembolism Based on Plasma Proteomics
- 2021
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Ingår i: Computational Methods in Systems Biology19th International Conference, CMSB 2021, Bordeaux, France, September 22–24, 2021, Proceedings. - Cham : Springer Science and Business Media Deutschland GmbH. ; , s. 108-121
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Konferensbidrag (refereegranskat)abstract
- Venous thromboembolism (VTE) is the third most common cardiovascular disease, affecting ∼ 1,000,000 individuals each year in Europe. VTE is characterized by an annual recurrent rate of ∼ 6%, and ∼ 30% of patients with unprovoked VTE will face a recurrent event after a six-month course of anticoagulant treatment. Even if guidelines recommend life-long treatment for these patients, about ∼ 70% of them will never experience a recurrence and will receive unnecessary lifelong anti-coagulation that is associated with increased risk of bleeding and is highly costly for the society. There is then urgent need to identify biomarkers that could distinguish VTE patients with high risk of recurrence from low-risk patients. Capitalizing on a sample of 913 patients followed up for the risk of VTE recurrence during a median of ∼ 10 years and profiled for 376 plasma proteomic antibodies, we here develop an artificial neural network (ANN) based strategy to identify a proteomic signature that helps discriminating patients at low and high risk of recurrence. In a first stage, we implemented a Repeated Editing Nearest Neighbors algorithm to select a homogeneous sub-sample of VTE patients. This sub-sample was then split in a training and a testing sets. The former was used for training our ANN, the latter for testing its discriminatory properties. In the testing dataset, our ANN led to an accuracy of 0.86 that compared to an accuracy of 0.79 as provided by a random forest classifier. We then applied a Deep Learning Important FeaTures (DeepLIFT) – based approach to identify the variables that contribute the most to the ANN predictions. In addition to sex, the proposed DeepLIFT strategy identified 6 important proteins (DDX1, HTRA3, LRG1, MAST2, NFATC4 and STXBP5) whose exact roles in the etiology of VTE recurrence now deserve further experimental validations.
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| 24. |
- Schmidt, David E., et al.
(författare)
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Clinical Implications of Discrepancy between One-Stage Clotting and Chromogenic Factor IX Activity in Hemophilia B
- 2024
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Ingår i: Thrombosis and Haemostasis. - : GEORG THIEME VERLAG KG. - 0340-6245 .- 2567-689X. ; 124:01, s. 032-039
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Tidskriftsartikel (refereegranskat)abstract
- Background Discrepancy in factor IX activity (FIX:C) between one-stage assay (OSA) and chromogenic substrate assay (CSA) in patients with hemophilia B (PwHB) introduces challenges for clinical management.Aim To study the differences in FIX:C using OSA and CSA in moderate and mild hemophilia B (HB), their impact on classification of severity, and correlation with genotype.Methods Single-center study including 21 genotyped and clinically characterized PwHB. FIX:C by OSA was measured using ActinFSL (Siemens) and CSA by Biophen (Hyphen). In addition, in vitro experiments with wild-type FIX were performed. Reproducibility of CSA was assessed between three European coagulation laboratories.Results FIX:C by CSA was consistently lower than by OSA, with 10/17 PwHB having a more severe hemophilia type by CSA. OSA displayed a more accurate description of the clinical bleeding severity, compared with CSA. A twofold difference between OSA:CSA FIX:C was present in 12/17 PwHB; all patients had genetic missense variants in the FIX serine protease domain. Discrepancy was also observed with diluted normal plasma, most significant for values below 0.10 IU/mL. Assessment of samples with low FIX:C showed excellent reproducibility of the CSA results between the laboratories.Conclusion FIX:C was consistently higher by OSA compared with the CSA. Assessing FIX:C by CSA alone would have led to diagnosis of a more severe hemophilia type in a significant proportion of patients. Our study suggests using both OSA and CSA FIX:C together with genotyping to classify HB severity and provide essential information for clinical management.
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| 25. |
- Yuan, Shuai, et al.
(författare)
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Anti-inflammatory diet and incident peripheral artery disease : Two prospective cohort studies
- 2022
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 41:6, s. 1191-1196
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Systemic inflammation plays a role in peripheral artery disease (PAD), and therefore, an anti-inflammatory diet may reduce PAD risk. We examined the association between the antiinflammatory diet and PAD risk by smoking status, a trigger of systemic inflammation. Methods: The study was based on two cohorts of 82 295 Swedish adults aged 45-83 years (38 823 women from Swedish Mammography Cohort and 45 472 men from Cohort of Swedish Men). An antiinflammatory diet index (AIDI; 0-17 scores) was used to estimate the anti-inflammatory potential of diet. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Over a median 22-year (interquartile range 7.5 years) follow-up period, 3413 PAD cases were ascertained. Compared with individuals in the lowest quartile of the AIDI (score <4), the HR of PAD for those in the highest quartile (score >8) was 0.84 (95% CI, 0.74-0.94). The inverse association was observed in current and past smokers but not in never smokers. The HR of PAD comparing extreme quartiles of the AIDI was 0.67 (95% CI, 0.53-0.86) in current smoker, 0.78 (95% CI, 0.63-0.97) in past smoker, and 1.00 (95% CI, 0.82-1.23) in never smokers. Among foods included in AIDI, high consumption of breakfast cereals, chocolate, red wine, and olive/canola oil, and low consumption of processed red meat and organ meats were associated with low PAD risk. Conclusions: The study suggests that adherence to a diet with high anti-inflammatory potential may lower PAD risk, especially in smokers. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 26. |
- Yuan, Shuai, et al.
(författare)
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Anti-inflammatory diet and venous thromboembolism : Two prospective cohort studies
- 2021
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier. - 0939-4753 .- 1590-3729. ; 31:10, s. 2831-2838
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Inflammation has been revealed to facilitate thrombogenesis and to increase the risk of venous thromboembolism (VTE). However, limited data are available on the association between the anti-inflammatory diet and incident VTE. We conducted a cohort analysis to examine this association and to further examine whether this association is modified by smoking status, a trigger of systemic inflammation.Methods and results: We used data from two cohorts including 81,507 middle-aged and older Swedish adults without previous VTE at baseline. An empirically validated anti-inflammatory diet index (AIDI), based on 12 foods with anti-inflammatory potential and 5 foods with pro-inflammatory potential, was employed to estimate the anti-inflammatory potential of diet. Haz-ard ratios (HRs), with corresponding 95% confidence intervals (CIs), of VTE were estimated by Cox proportional hazards regression models. During a mean follow-up of 17.8-years, 5241 VTE cases were diagnosed. Compared with individuals in the lowest quartile of the AIDI (score 4), those in the highest quartile (score 8) had a 9% (95% CI, 0-17%) lower risk of VTE. The in-verse association was observed in current and past smokers (HR between the two extreme quar-tiles, 0.80, 95% CI, 0.70-0.91) but not in never smokers (HR, 1.03, 95% CI, 0.91-1.17). French fries (HR per serving, 1.33, 95% CI, 1.06, 1.67) but no other foods included in AIDI was associated with VTE.Conclusion: The study suggests that a consumption of foods with high anti-inflammatory poten-tial may play a role in the prevention of VTE in smokers.
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| 27. |
- Yuan, Shuai, et al.
(författare)
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Cardiometabolic, Lifestyle, and Nutritional Factors in Relation to Varicose Veins : A Mendelian Randomization Study.
- 2021
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Ingår i: Journal of the American Heart Association. - : Wolters Kluwer. - 2047-9980. ; 10:21
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Tidskriftsartikel (refereegranskat)abstract
- Background: We conducted a 2-sample Mendelian randomization study to assess the associations of cardiometabolic, lifestyle, and nutritional factors with varicose veins.Methods and Results: Independent single-nucleotide polymorphisms associated with height (positive control), body mass index, type 2 diabetes, diastolic and systolic blood pressure, smoking, alcohol and coffee consumption, 7 circulating vitamins (A, B6, B9, B12, C, 25-hydroxyvitamin D, and E), and 5 circulating minerals (calcium, iron, magnesium, selenium, and zinc) at the genome-wide significance level were used as instrumental variables. Summary-level data for the genetic associations with varicose veins were obtained from the UK Biobank (8763 cases and 352 431 noncases) and the FinnGen consortium (13 928 cases and 153 951 noncases). Genetically predicted higher height, body mass index, smoking, and circulating iron levels were associated with an increased risk of varicose veins. The odds ratios (ORs) per 1-SD increase in the exposure were 1.34 (95% CI, 1.25–1.43) for height, 1.39 (95% CI, 1.27–1.52) for body mass index, 1.12 (95% CI, 1.04–1.22) for the prevalence of smoking initiation, and 1.24 (95% CI, 1.16–1.33) for iron. Higher genetically predicted systolic blood pressure and circulating calcium and zinc levels were associated with a reduced risk of varicose veins, whereas the association for systolic blood pressure did not persist after adjustment for genetically predicted height. The OR was 0.75 (95% CI, 0.62–0.92) per 1-SD increase in calcium levels and 0.97 (95% CI, 0.95–0.98) for zinc.Conclusions: This study identified several modifiable risk factors for varicose veins.
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| 28. |
- Yuan, Shuai, et al.
(författare)
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Causal effect of renal function on venous thromboembolism : a two-sample Mendelian randomization investigation
- 2022
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Nature. - 0929-5305 .- 1573-742X. ; 53:1, s. 43-50
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Tidskriftsartikel (refereegranskat)abstract
- Whether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10-8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.
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| 29. |
- Yuan, Shuai, et al.
(författare)
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Effects of tumour necrosis factor on cardiovascular disease and cancer : A two-sample Mendelian randomization study
- 2020
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Ingår i: EBioMedicine. - : ELSEVIER. - 2352-3964. ; 59
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tumour necrosis factor (TNF) inhibitors are used in the treatment of certain autoimmune diseases but given the role of TNF in tumour biology and atherosclerosis, such therapies may influence the risk of cancer and cardiovascular disease. We conducted a Mendelian randomization study to explore whether TNF levels are causally related to cardiovascular disease and cancer.Methods: Single-nucleotide polymorphisms associated with TNF levels at genome-wide significance were identified from a genome-wide association study of 30 912 European-ancestry individuals. Three TNF-associated single-nucleotide polymorphisms associated with higher risk of autoimmune diseases were used as instrumental variables. Summary-level data for 14 cardiovascular diseases, overall cancer and 14 site-specific cancers were obtained from UK Biobank and consortia.Findings: Genetically-predicted TNF levels were positively associated with coronary artery disease (odds ratio (OR) 2.25; 95% confidence interval (CI) 1.50, 3.37) and ischaemic stroke (OR 2.27; 95% CI 1.50, 3.43), and inversely associated with overall cancer (OR 0.54; 95% CI 0.42, 0.69), breast cancer (OR 0.51; 95% CI 0.39, 0.67), and colorectal cancer (OR 0.20; 95% CI 0.09, 0.45). There were suggestive associations of TNF with venous thromboembolism (OR 2.18; 95% CI 1.32, 3.59), endometrial cancer (OR 0.25; 95% CI 0.07, 0.94), and lung cancer (OR 0.45; 95% CI 0.21, 0.94).Interpretation: This study found evidence of causal associations of increased TNF levels with higher risk of common cardiovascular diseases and lower risk of overall and certain cancers.
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| 30. |
- Yuan, Shuai, et al.
(författare)
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Lifestyle factors and venous thromboembolism in two cohort studies
- 2021
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Ingår i: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 202, s. 119-124
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Evidence on the associations of lifestyle factors with venous thromboembolism (VTE) is inconsistent. We aimed to investigate the associations of modifiable lifestyle factors with VTE in women and men. Methods: We used data from two cohorts comprising 30,137 women and 36,193 men aged over 45 years and free of cancer and VTE. Information on lifestyle factors was collected in 1997 via a self-administrated questionnaire. VTE cases were ascertained by linkage with the National Patient Register until the end of 2019. Results: During a mean of 16.9-years follow-up, 1784 women and 2043 men were diagnosed with VTE. Compared with individuals with <10 min/day of physical activity, the multivariable hazard ratios (HRs) of VTE were 0.67 (95% confidence interval (CI), 0.58, 0.79) and 0.78 (95% CI, 0.67, 0.92) in women and men with >60 min/day, respectively. Compared with individuals with the lowest adherence to a modified Dietary Approaches to Stop Hypertension diet, the multivariable HRs of VTE were 0.87 (95% CI, 0.75, 0.99) and 0.88 (95% CI, 0.80, 1.00) for women and men with the highest adherence. In women, the multivariable HRs of VTE were 1.16 (95% CI, 1.03, 1.29) for past smoker and 1.28 (95% CI, 1.14, 1.45) for current smoker compared with never smoker. Alcohol and coffee consumption were not associated with VTE. Conclusions: This study suggests that being physically active and adhering to a healthy diet may lower the risk of VTE in women and men. Cigarette smoking was positively associated with VTE in women.
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| 31. |
- Yuan, Shuai, et al.
(författare)
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Overall and abdominal obesity in relation to venous thromboembolism
- 2021
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Ingår i: Journal of Thrombosis and Haemostasis. - : John Wiley & Sons. - 1538-7933 .- 1538-7836. ; 19:2, s. 460-469
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Abdominal obesity has been shown to be a superior measure over overall obesity for detecting cardiovascular risk.OBJECTIVE: We conducted this study to compare the effects of overall and central obesity on VTE and to calculate population attributable fraction for obesity for VTE.METHODS: Body mass index (BMI) and waist circumference (WC) was used to represent overall and abdominal obesity, respectively. In the cohort study, we included 74,317 Swedish adults with anthropometric measures in 1997 and of whom 4332 were diagnosed with VTE until the end of 2017. A Mendelian randomization study was conducted to investigate causal associations of BMI, WC, and WC adjusted for BMI with VTE using data from FinnGen and UK Biobank study. Population attributable fraction was calculated for overall and abdominal obesity for VTE.RESULTS: In the cohort study, there were dose-response associations of BMI and WC with VTE. The association between BMI and VTE was attenuated largely after adjusting for WC. Among individuals with normal BMI, participants with substantially increased WC had 53% higher (HR 1.53; 95% CI, 1.28, 1.81) risk of VTE compared with those with normal WC. The causality of the association of WC adjusted for BMI with VTE was confirmed in MR analysis. The estimated population-attributable risk due to elevated BMI and WC were 12.4% (8.4%, 16.5%) and 23.7% (18.1%, 29.4%), respectively.CONCLUSIONS: WC might be a preferable indictor linking obesity to VTE. A large proportion of VTE cases can be prevented if the population maintained a healthy BMI and WC.
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| 32. |
- Yuan, Shuai, et al.
(författare)
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Plasma Phospholipid Fatty Acids and Risk of Venous Thromboembolism : Mendelian Randomization Investigation
- 2022
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 14:16
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Tidskriftsartikel (refereegranskat)abstract
- Circulating fatty acids may affect thrombosis but epidemiological data on the associations between fatty acids and risk of venous thromboembolism (VTE) are limited and conflicting. We conducted a Mendelian randomization study to examine the causal associations of 10 circulating fatty acids with VTE risk. Genetic variants strongly associated with ten fatty acids and without linkage disequilibrium were selected as instrumental variables from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Genetic associations for VTE and its subtypes were obtained from the International Network Against Venous Thrombosis Consortium (30,234 cases and 172,122 controls) and the FinnGen study (11,288 VTE cases and 254,771 controls). Estimates from the two data sources were combined. Per standard deviation increase in genetically predicted fatty acid levels, the combined odds ratio (OR) of VTE was 0.88 (95% confidence interval [CI] 0.84-0.92) for alpha-linolenic acid, 0.92 (95% CI 0.90-0.95) for linoleic acid, 0.85 (95% CI 0.78-0.92) for palmitoleic acid, 0.77 (95% CI 0.77-0.84) for oleic acid, 1.16 (95% CI 1.10-1.23) for eicosapentaenoic acid, 1.10 (95% CI 1.06-1.14) for docosapentaenoic acid, 1.06 (95% CI 1.04-1.08) for arachidonic acid, and 1.19 (95% CI 1.11-1.28) for stearic acid. Genetically predicted levels of docosahexaenoic acid or palmitoleic acid were not associated with VTE risk. Four and eight out of ten genetically predicted fatty acid levels were associated with risk of pulmonary embolism and deep vein thrombosis, respectively. This study suggests that strategies targeting at fatty acids may act as prevention approaches for VTE.
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| 33. |
- Yuan, Shuai, et al.
(författare)
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Plasma Phospholipid Fatty Acids, FADS1 and Risk of 15 Cardiovascular Diseases : A Mendelian Randomisation Study
- 2019
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMp1usC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the FADS1 gene were associated with most FAs. We performed a secondary analysis of the association between a functional variant (rs174547) in FADS1, which encodes Delta 5-desaturase (a key enzyme in the endogenous FA synthesis), and CVD. Genetic predisposition to higher plasma alpha-linolenic, linoleic, and oleic acid levels was associated with lower odds of large-artery stroke and venous thromboembolism, whereas higher arachidonic and stearic acid levels were associated with higher odds of these two CVDs. The associations were driven by SNPs in or close to FADS1. In the secondary analysis, the minor allele of rs174547 in FADS1 was associated with significantly lower odds of any ischemic stroke, large-artery stroke, and venous thromboembolism and showed suggestive evidence of inverse association with coronary artery disease, abdominal aortic aneurysm and aortic valve stenosis. Genetically higher plasma alpha-linolenic, linoleic, and oleic acid levels are inversely associated with large-artery stroke and venous thromboembolism, whereas arachidonic and stearic acid levels are positively associated with these CVDs. The associations were driven by FADS1, which was also associated with other CVDs.
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| 34. |
- Yuan, Shuai, et al.
(författare)
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Plasma protein and venous thromboembolism : prospective cohort and mendelian randomisation analyses.
- 2023
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141.
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Tidskriftsartikel (refereegranskat)abstract
- We conducted cohort and Mendelian randomisation (MR) analyses to examine the associations of circulating proteins with risk of venous thromboembolism (VTE) to provide evidence basis for disease prevention and drug development. Cohort analysis was performed in 11 803 participants without baseline VTE. Cox regression was used to estimate the associations between 257 proteins and VTE risk. A machine-learning model was constructed to compare the importance of identified proteins and traditional risk factors. Genetic association data on VTE were obtained from a genome-wide meta-analysis (26 066 cases and 624 053 controls) and FinnGen (14 454 cases and 294 700 controls). The cohort analysis, including 353 incident VTE cases diagnosed during a 6.6-year follow-up, identified 21 proteins associated with VTE risk after false discovery rate correction. The machine-learning model indicated that body mass index and von Willebrand factor (vWF) made the same as well as most of the contributions to the overall model prediction. MR analysis found that genetically predicted levels of vWF, SERPINE1 (plasminogen activator inhibitor 1, known as PAI-1), EPHB4 (ephrin type-B receptor 4), TYRO3 (tyrosine-protein kinase receptor TYRO3), TNFRSF11A (tumour necrosis factor receptor superfamily member 11A), and BOC (brother of CDO) were causally associated with VTE risk.
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| 35. |
- Yuan, Shuai, et al.
(författare)
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Ultra-processed food intake and incident venous thromboembolism risk : Prospective cohort study
- 2023
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 42:8, s. 1268-1275
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Ultra-processed food (UPF) intake has been associated with multiple health outcomes, but data on the association between UPF intake and venous thromboembolism (VTE) risk are lacking. We conducted this study to examine the association between UPF intake and the risk of incident VTE.Methods: This prospective cohort study was based on 186,323 participants free of baseline VTE from the UK Biobank. UPF intake was assessed by 24-h recall questionnaires. Data on incident VTE came from the nationwide inpatient and primary care datasets and the death registry. Cox proportional hazards regression was used to estimate the association between UPF intake and incident VTE risk. Multiplicative interactions and stratified analyses by age, sex, and body mass index were performed.Results: During a 10.5-year (median) follow-up, 4235 incident VTE cases were diagnosed. After adjusting for covariates, the hazard ratio of VTE among individuals with the highest quintile of UPF intake was 1.05 (95% confidence interval [CI] 0.94, 1.17) for UPF in servings, 1.12 (95% CI 1.01, 1.24) in grams, 1.10 (95% CI 1.00, 1.22) in grams %, 1.21 (95% CI 1.10, 1.33) in energy, and 1.15 (95% CI 1.05, 1.27) in energy % compared to those in the lowest quintile. Age, sex, and body mass index did not modify the associations (Pinteraction > 0.05).Conclusions: Higher UPF intake was associated with a moderately increased risk of VTE.
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