| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 5. |
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| 6. |
- Tabassum, R, et al.
(författare)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 7. |
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| 8. |
- Kurki, MI, et al.
(författare)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Tidskriftsartikel (refereegranskat)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Andersen, M. S., et al.
(författare)
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To facilitate a fair bioeconomy transition, stronger regional-level linkages are needed
- 2022
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Ingår i: Biofuels Bioproducts & Biorefining-Biofpr. - : Wiley. - 1932-104X .- 1932-1031. ; 16:4, s. 929-941
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Tidskriftsartikel (refereegranskat)abstract
- The great hopes in Brussels that a circular bioeconomy will help bridge the growing divide between urban and rural areas and allow the hinterlands to prosper from 'green growth' are addressed in this article, which reflects on insights from three Nordic case studies of brown, green and blue biomass use at different levels of technology readiness. A closer examination of the forward, backward, fiscal and final demand linkages at regional level from increased biomass utilization, from eastern Finland and northern Sweden to Jutland and North Atlantic islands, suggests that linkages are and will remain relatively weak, predominantly dashing the expectations. As suppliers and exporters of natural resources, disadvantaged regions may all too easily get locked into a 'staples trap', where the value creation evaporates owing in part to the steep start-up costs and the associated boom-and-bust cycles, which place them in a weak position vis-a-vis the resource manufacturers and consumers. To make the prospects of development, employment and prosperity in the hinterlands materialize, measures are needed to strengthen the regional-level economic linkages. Regional-level revolving funds based on benefit-sharing instruments related to natural resources can be used to bolster economic development, as reflected in such schemes present in both China and Canada. We call for further research into whether and how such approaches can be replicated successfully by channeling revenues from biomass cultivation to regional-scale revolving funds, with mandates to strengthen long-term economic linkages and prosperity within the hinterlands. (c) 2022 The Authors. Biofuels, Bioproducts and Biorefining published by Society of Industrial Chemistry and John Wiley & Sons Ltd
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| 13. |
- Bhattacharya, S. K., et al.
(författare)
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5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: A cluster-randomised, double-blind, placebo-controlled trial
- 2013
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Ingår i: Lancet. Infectious Diseases. - 1473-3099 .- 1474-4457. ; 13:12, s. 1050-1056
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. Methods: In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. Findings: 69 of 31932 recipients of vaccine and 219 of 34968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy. Interpretation: Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Funding: Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. © 2013 Elsevier Ltd.
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| 14. |
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| 15. |
- Feldhoff, J. H., et al.
(författare)
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Geometric signature of complex synchronisation scenarios
- 2013
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Ingår i: Europhysics letters. - : IOP Publishing. - 0295-5075 .- 1286-4854. ; 102:3, s. 30007-
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Tidskriftsartikel (refereegranskat)abstract
- Synchronisation between coupled oscillatory systems is a common phenomenon in many natural as well as technical systems. Varying the coupling strength often leads to qualitative changes in the dynamics exhibiting different types of synchronisation. Here, we study the geometric signatures of coupling along with the onset of generalised synchronisation (GS) between two coupled chaotic oscillators by mapping the systems' individual as well as joint recurrences in phase space to a complex network. For a paradigmatic continuous-time model system, we show that the transitivity properties of the resulting joint recurrence networks display distinct variations associated with changes in the structural similarity between different parts of the considered trajectories. They therefore provide a useful new indicator for the emergence of GS.
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| 16. |
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| 17. |
- Kaukonen, M, et al.
(författare)
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A missense variant in IFT122 associated with a canine model of retinitis pigmentosa
- 2021
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Ingår i: Human genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 140:11, s. 1569-1579
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Tidskriftsartikel (refereegranskat)abstract
- Retinitis pigmentosa (RP) is a blinding eye disease affecting nearly two million people worldwide. Dogs are affected with a similar illness termed progressive retinal atrophy (PRA). Lapponian herders (LHs) are affected with several types of inherited retinal dystrophies, and variants in PRCD and BEST1 genes have been associated with generalized PRA and canine multifocal retinopathy 3 (cmr3), respectively. However, all retinal dystrophy cases in LHs are not explained by these variants, indicating additional genetic causes of disease in the breed. We collected DNA samples from 10 PRA affected LHs, with known PRCD and BEST1 variants excluded, and 34 unaffected LHs. A genome-wide association study identified a locus on CFA20 (praw = 2.4 × 10–7, pBonf = 0.035), and subsequent whole-genome sequencing of an affected LH revealed a missense variant, c.3176G>A, in the intraflagellar transport 122 (IFT122) gene. The variant was also found in Finnish Lapphunds, in which its clinical relevancy needs to be studied further. The variant interrupts a highly conserved residue, p.(R1059H), in IFT122 and likely impairs its function. Variants in IFT122 have not been associated with retinal degeneration in mammals, but the loss of ift122 in zebrafish larvae impaired opsin transport and resulted in progressive photoreceptor degeneration. Our study establishes a new spontaneous dog model to study the role of IFT122 in RP biology, while the affected breed will benefit from a genetic test for a recessive condition.
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| 18. |
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| 19. |
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| 20. |
- Radebach, A., et al.
(författare)
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Disentangling different types of El Nino episodes by evolving climate network analysis
- 2013
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Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics. - 1539-3755 .- 1550-2376. ; 88:5, s. 052807-
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Tidskriftsartikel (refereegranskat)abstract
- Complex network theory provides a powerful toolbox for studying the structure of statistical interrelationships between multiple time series in various scientific disciplines. In this work, we apply the recently proposed climate network approach for characterizing the evolving correlation structure of the Earth's climate system based on reanalysis data for surface air temperatures. We provide a detailed study of the temporal variability of several global climate network characteristics. Based on a simple conceptual view of red climate networks (i.e., networks with a comparably low number of edges), we give a thorough interpretation of our evolving climate network characteristics, which allows a functional discrimination between recently recognized different types of El Nino episodes. Our analysis provides deep insights into the Earth's climate system, particularly its global response to strong volcanic eruptions and large-scale impacts of different phases of the El Nino Southern Oscillation.
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| 21. |
- Thomasson, Magnus, 1961, et al.
(författare)
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Formation of leading spiral arms in retrograde galaxy encounters
- 1989
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 211:1, s. 25-36
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Tidskriftsartikel (refereegranskat)abstract
- The formation of spiral structures in retrograde galaxy encounters was studied theoretically and with N-body simulations. A one-armed leading spiral dominates in a disk if the tidal perturbation from the retrograde companion is large enough, and the disk is surrounded by a massive halo. The leading arm is made up of particles in slightly elongated orbits, the turning points of which outline the arm. The orbits precess in such a way that the arm structure survives while it rotates in the opposite sense to the disk rotation. From the literature it is found that very few spirals in a sample of galaxies with a large companion have leading spiral arms. A possible reason for this is that very few spiral galaxies have a halo with larger mass than the disk mass.
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| 22. |
- Aerts, Marc, et al.
(författare)
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Pooled individual patient data from five countries were used to derive a clinical prediction rule for coronary artery disease in primary care.
- 2017
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier. - 0895-4356 .- 1878-5921. ; 81, s. 120-128
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To construct a clinical prediction rule for coronary artery disease (CAD) presenting with chest pain in primary care.STUDY DESIGN AND SETTING: Meta-Analysis using 3,099 patients from five studies. To identify candidate predictors, we used random forest trees, multiple imputation of missing values, and logistic regression within individual studies. To generate a prediction rule on the pooled data, we applied a regression model that took account of the differing standard data sets collected by the five studies.RESULTS: The most parsimonious rule included six equally weighted predictors: age ≥55 (males) or ≥65 (females) (+1); attending physician suspected a serious diagnosis (+1); history of CAD (+1); pain brought on by exertion (+1); pain feels like "pressure" (+1); pain reproducible by palpation (-1). CAD was considered absent if the prediction score is <2. The area under the ROC curve was 0.84. We applied this rule to a study setting with a CAD prevalence of 13.2% using a prediction score cutoff of <2 (i.e., -1, 0, or +1). When the score was <2, the probability of CAD was 2.1% (95% CI: 1.1-3.9%); when the score was ≥ 2, it was 43.0% (95% CI: 35.8-50.4%).CONCLUSIONS: Clinical prediction rules are a key strategy for individualizing care. Large data sets based on electronic health records from diverse sites create opportunities for improving their internal and external validity. Our patient-level meta-analysis from five primary care sites should improve external validity. Our strategy for addressing site-to-site systematic variation in missing data should improve internal validity. Using principles derived from decision theory, we also discuss the problem of setting the cutoff prediction score for taking action.
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| 23. |
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| 24. |
- Brunelli, M., et al.
(författare)
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Experimental Determination of Irreversible Entropy Production in out-of-Equilibrium Mesoscopic Quantum Systems
- 2018
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 121:16
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Tidskriftsartikel (refereegranskat)abstract
- By making use of a recently proposed framework for the inference of thermodynamic irreversibility in bosonic quantum systems, we experimentally measure and characterize the entropy production rates in the nonequilibrium steady state of two different physical systems a micromechanical resonator and a Bose-Einstein condensate each coupled to a high finesse cavity and hence also subject to optical loss. Key features of our setups, such as the cooling of the mechanical resonator and signatures of a structural quantum phase transition in the condensate, are reflected in the entropy production rates. Our work demonstrates the possibility to explore irreversibility in driven mesoscopic quantum systems and paves the way to a systematic experimental assessment of entropy production beyond the microscopic limit.
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| 25. |
- Chien, Yin-Hsiu, et al.
(författare)
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Mudd's disease (MAT I/III deficiency) : a survey of data for MAT1A homozygotes and compound heterozygotes
- 2015
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: This paper summarizes the results of a group effort to bring together the worldwide available data on patients who are either homozygotes or compound heterozygotes for mutations in MAT1A. MAT1A encodes the subunit that forms two methionine adenosyltransferase isoenzymes, tetrameric MAT I and dimeric MAT III, that catalyze the conversion of methionine and ATP to S-adenosylmethionine (AdoMet). Subnormal MAT I/III activity leads to hypermethioninemia. Individuals, with hypermethioninemia due to one of the MAT1A mutations that in heterozygotes cause relatively mild and clinically benign hypermethioninemia are currently often being flagged in screening programs measuring methionine elevation to identify newborns with defective cystathionine beta-synthase activity. Homozygotes or compound heterozygotes for MAT1A mutations are less frequent. Some but not all, such individuals have manifested demyelination or other CNS abnormalities. Purpose of the study: The goals of the present effort have been to determine the frequency of such abnormalities, to find how best to predict whether they will occur, and to evaluate the outcomes of the variety of treatment regimens that have been used. Data have been gathered for 64 patients, of whom 32 have some evidence of CNS abnormalities (based mainly on MRI findings), and 32 do not have such evidence. Results and Discussion: The results show that mean plasma methionine concentrations provide the best indication of the group into which a given patient will fall: those with means of 800 mu M or higher usually have evidence of CNS abnormalities, whereas those with lower means usually do not. Data are reported for individual patients for MAT1A genotypes, plasma methionine, total homocysteine (tHcy), and AdoMet concentrations, liver function studies, results of 15 pregnancies, and the outcomes of dietary methionine restriction and/or AdoMet supplementation. Possible pathophysiological mechanisms that might contribute to CNS damage are discussed, and tentative suggestions are put forth as to optimal management.
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