| 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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| 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. |
- 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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| 6. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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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. |
- 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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| 10. |
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| 11. |
- Sur, Dipika, et al.
(författare)
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Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial.
- 2009
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Ingår i: Lancet. - 1474-547X. ; 374:9702, s. 1694-702
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oral cholera vaccines consisting of killed whole cells have been available for many years, but they have not been used extensively in populations with endemic disease. An inexpensive, locally produced oral killed-whole-cell vaccine has been used in high-risk areas in Vietnam. To expand the use of this vaccine, it was modified to comply with WHO standards. We assessed the efficacy and safety of this modified vaccine in a population with endemic cholera. METHODS: In this double-blind trial, 107 774 non-pregnant residents of Kolkata, India, aged 1 year or older, were cluster-randomised by dwelling to receive two doses of either modified killed-whole-cell cholera vaccine (n=52 212; 1966 clusters) or heat-killed Escherichia coli K12 placebo (n=55 562; 1967 clusters), both delivered orally. Randomisation was done by computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for the patient to seek treatment in a health-care facility. We undertook an interim, per-protocol analysis at 2 years of follow-up that included individuals who received two completely ingested doses of vaccine or placebo. We assessed first episodes of cholera that occurred between 14 days and 730 days after receipt of the second dose. This study is registered with ClinicalTrials.gov, number NCT00289224. FINDINGS: 31 932 participants assigned to vaccine (1721 clusters) and 34 968 assigned to placebo (1757 clusters) received two doses of study treatment. There were 20 episodes of cholera in the vaccine group and 68 episodes in the placebo group (protective efficacy 67%; one-tailed 99% CI, lower bound 35%, p<0.0001). The vaccine protected individuals in age-groups 1.0-4.9 years, 5.0-14.9 years, and 15 years and older, and protective efficacy did not differ significantly between age-groups (p=0.28). We recorded no vaccine-related serious adverse events. INTERPRETATION: This modified killed-whole-cell oral vaccine, compliant with WHO standards, is safe, provides protection against clinically significant cholera in an endemic setting, and can be used in children aged 1.0-4.9 years, who are at highest risk of developing cholera in endemic settings. FUNDING: Bill & Melinda Gates Foundation, Swedish International Development Cooperation Agency, Governments of South Korea, Sweden, and Kuwait.
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| 12. |
- Chittani, Martina, et al.
(författare)
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TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.
- 2015
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Ingår i: Journal of Hypertension. - 1473-5598. ; 33:6, s. 1301-1309
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Tidskriftsartikel (refereegranskat)abstract
- Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects.
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| 13. |
- Donges, Jonathan F., et al.
(författare)
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Non-linear regime shifts in Holocene Asian monsoon variability : potential impacts on cultural change and migratory patterns
- 2015
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 11:5, s. 709-741
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Tidskriftsartikel (refereegranskat)abstract
- The Asian monsoon system is an important tipping element in Earth's climate with a large impact on human societies in the past and present. In light of the potentially severe impacts of present and future anthropogenic climate change on Asian hydrology, it is vital to understand the forcing mechanisms of past climatic regime shifts in the Asian monsoon domain. Here we use novel recurrence network analysis techniques for detecting episodes with pronounced non-linear changes in Holocene Asian monsoon dynamics recorded in speleothems from caves distributed throughout the major branches of the Asian monsoon system. A newly developed multi-proxy methodology explicitly considers dating uncertainties with the COPRA (COnstructing Proxy Records from Age models) approach and allows for detection of continental-scale regime shifts in the complexity of monsoon dynamics. Several epochs are characterised by non-linear regime shifts in Asian monsoon variability, including the periods around 8.5-7.9, 5.7-5.0, 4.1-3.7, and 3.0-2.4 ka BP. The timing of these regime shifts is consistent with known episodes of Holocene rapid climate change (RCC) and high-latitude Bond events. Additionally, we observe a previously rarely reported non-linear regime shift around 7.3 ka BP, a timing that matches the typical 1.0-1.5 ky return intervals of Bond events. A detailed review of previously suggested links between Holocene climatic changes in the Asian monsoon domain and the archaeological record indicates that, in addition to previously considered longer-term changes in mean monsoon intensity and other climatic parameters, regime shifts in monsoon complexity might have played an important role as drivers of migration, pronounced cultural changes, and the collapse of ancient human societies.
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| 14. |
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| 15. |
- Donner, K.J., et al.
(författare)
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Structure and evolution of long-lived spiral patterns in galaxies
- 1994
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 290, s. 785-795
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Tidskriftsartikel (refereegranskat)abstract
- We use N-body simulations to study the non-linear evolution of spontaneous and tidally induced spiral patterns in galaxies on time-scales of several rotation periods of the disc. We find that the patterns can sometimes survive with an almost constant amplitude for five revolutions or more, and tend to be regenerated after disappearing temporarily. The pattern velocity is such that the corotation radius is where the self-gravity as measured by the swing amplification of the m=2 component is strongest, and the amplitude of the pattern is larger when swing amplification is stronger. The shape of the spirals is independent of the origin of the pattern, and corresponds to the critical wave number kappa^2^/(2piGmu), where mu is the disc surface density. The pattern survives longer if the self-gravity of the disc is strong. For a given disc model the life-time of the pattern depends on its amplitude, with stronger patterns having shorter life-times. If self-gravity is weak, the dominant tidal effect is a kinematic spiral at the inner Lindblad resonance.
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| 16. |
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| 17. |
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| 18. |
- 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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| 19. |
- Kuz'min, M. D., et al.
(författare)
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Magnetic anisotropy of La2Co7
- 2015
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 118:5
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Tidskriftsartikel (refereegranskat)abstract
- A magnetization study of a La2Co7 single crystal has obtained the following anisotropy constants: K-1 = 1.4 MJ/m(3) and K-2 = 0.02 MJ/m(3) (at room temperature). The corresponding anisotropy field is 6.7 T; an earlier report of a much higher value (17 T) has not been confirmed. A significant (10%) magnetization anisotropy has been observed. Density-functional calculations are in qualitative agreement with the new data. (C) 2015 AIP Publishing LLC.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Thomasson, Magnus, 1961, et al.
(författare)
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A computer-generated galaxy model with long-lived two-armed spiral structure
- 1990
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 356, s. L9-L13
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Tidskriftsartikel (refereegranskat)abstract
- A long-lived two-armed spiral has been generated in an N-body computer simulation of a galaxy with a static bulge and halo and an active disk composed of 60,000 particles. The spiral lasts for about three pattern revolutions without severe distortion and persists for at least two more revolutions with distortions and bifurcations resulting from an increasingly clumpy ISM. This suggests that two-armed grand design spirals in nonbarred noninteracting galaxies can be long-lived if star formation and other heat sources not present in the simulation maintain a steady interstellar medium.
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| 26. |
- 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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| 27. |
- Thomasson, Magnus, 1961, et al.
(författare)
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Simulations of the effect of spiral arms on the cloud-ensemble velocity dispersion
- 1991
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 250:2, s. 316-323
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Tidskriftsartikel (refereegranskat)abstract
- N-body simulations are used to study the effect of spiral heating, viscous heating, and cooling by inelastic collisions on the molecular cloud ensemble velocity dispersion. The simulations include inelastic collisions between clouds as well as long-range gravitational forces. The theory for heating and cooling of the cloud population is described, and the numerical code and the galaxy model are examined. Spiral arms not only heat the cloud population, they also cause increased cooling due to the large number of cloud-cloud collisions in the arms. It is found that the heating dominates, in that a stronger spiral potential leads to a higher velocity dispersion. The spiral potential is stronger for smaller values of Q(star). The steady-state cloud-ensemble velocity dispersion is found to be constant with the radius. Its value for a typical simulation of a multiple-arm spiral is slightly smaller than the value observed in the Galaxy. The stellar velocity dispersion corresponds to a radius-independent Q(star), for multiple-arm galaxies regardless of the initial radial dependence.
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| 28. |
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