| 1. |
- 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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| 2. |
- 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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| 3. |
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| 4. |
- 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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| 5. |
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| 6. |
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| 7. |
- Le, S., et al.
(författare)
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Differences in cardiometabolic risk profiles between Chinese and Finnish older adults with glucose impairment and central obesity
- 2022
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Ingår i: Journal of Endocrinological Investigation. - : Springer. - 0391-4097 .- 1720-8386. ; 45:7, s. 1427-1437
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Tidskriftsartikel (refereegranskat)abstract
- Background Obesity and ethnicity play important roles in cardiovascular complications in patients with type 2 diabetes mellitus (T2DM). This study aimed to compare cardiometabolic risk profiles between Chinese and Finnish older adults of central obesity with prediabetes or T2DM.Methods Study subjects were 60-74 years old and originated from two population samples. The Finnish subjects came from the Kuopio Ischemic Heart Disease (KIHD) study (n = 1089), and the Chinese subjects came from the Shanghai High-risk Diabetic Screen (SHiDS) study (n = 818). The KIHD and SHiDS studies used similar questionnaires to determine participants' baseline characteristics regarding the history of medication use and diseases and lifestyle factors. All study subjects participated in glucose tolerance tests and anthropometry assessments, including waist circumference measurements.Results Among study subjects of central obesity with prediabetes (n = 298), fasting and 2-h glucose, and fasting insulin and insulin resistance were significantly higher in Chinese than in Finnish (p < 0.0001-0.016). In addition, triglyceride (TG) level was higher and the low-density lipoprotein cholesterol (LDL) and LDL to high-density lipoprotein cholesterol (HDL) ratio were lower in Chinese than in Finnish (p < 0.0001-0.003). Among subjects of central obesity with T2DM (n = 251), Chinese subjects had significantly less proportions of antihypertensive, glycaemic control medication, and statin users as well as lower level of physical activity (p < 0.0001 for all), while higher blood pressure (p = 0.002 for systolic blood pressure and p < 0.0001 for diastolic blood pressure), TG levels (p < 0.05) and HDL (p = 0.002) than the Finnish counterparts. There were no differences in beta-cell function (HOMA-beta) between Chinese and Finnish both in prediabetes and T2DM.Conclusions Our results indicated that Chinese and Finnish older adults of central obesity with prediabetes and T2DM had similar beta-cell function. However, Chinese individuals with prediabetes are prone to insulin resistance. Meanwhile, lipid metabolism dysfunction is also different between Chinese and Finnish. Chinese older adults of central obesity with prediabetes showed higher TG, but Finnish showed higher LDL and LDL/HDL. Strategic for T2DM prevention and treatment should be ethnically specific.
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| 8. |
- Peters, Ruth, et al.
(författare)
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An investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.
- 2020
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Ingår i: Neurology. - 1526-632X. ; 94:3
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.
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| 9. |
- Willeit, Peter, et al.
(författare)
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Natriuretic peptides and integrated risk assessment for cardiovascular disease : an individual-participant-data meta-analysis
- 2016
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 4:10, s. 840-849
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Tidskriftsartikel (refereegranskat)abstract
- Background: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. Methods: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7.5%, and >= 7.5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. Findings: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1.76 (95% CI 1.56-1.98) for the combination of coronary heart disease and stroke and 2.00 (1.77-2.26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0.012 (0.010-0.014) and a net reclassification improvement of 0.027 (0.019-0.036) for the combination of coronary heart disease and stroke and a C-index increase of 0.019 (0.016-0.022) and a net reclassification improvement of 0.028 (0.019-0.038) for the combination of coronary heart disease, stroke, and heart failure. Interpretation: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.
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| 10. |
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| 11. |
- Kuronen, A., et al.
(författare)
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Segregation, precipitation, and alpha-alpha ' phase separation in Fe-Cr alloys
- 2015
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 92:21
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Tidskriftsartikel (refereegranskat)abstract
- Iron-chromium alloys, the base components of various stainless steel grades, have numerous technologically and scientifically interesting properties. However, these features are not yet sufficiently understood to allow their full exploitation in technological applications. In this work, we investigate segregation, precipitation, and phase separation in Fe-Cr systems analyzing the physical mechanisms behind the observed phenomena. To get a comprehensive picture of Fe-Cr alloys as a function of composition, temperature, and time the present investigation combines Monte Carlo simulations using semiempirical interatomic potential, first-principles total energy calculations, and experimental spectroscopy. In order to obtain a general picture of the relation of the atomic interactions and properties of Fe-Cr alloys in bulk, surface, and interface regions several complementary methods have to be used. Using the exact muffin-tin orbitals method with the coherent potential approximation (CPA-EMTO) the effective chemical potential as a function of Cr content (0-15 at. % Cr) is calculated for a surface, second atomic layer, and bulk. At similar to 10 at. % Cr in the alloy the reversal of the driving force of a Cr atom to occupy either bulk or surface sites is obtained. The Cr-containing surfaces are expected when the Cr content exceeds similar to 10 at. %. The second atomic layer forms about a 0.3 eV barrier for the migration of Cr atoms between the bulk and surface atomic layer. To get information on Fe-Cr in larger scales we use semiempirical methods. However, for Cr concentration regions less than 10 at. %, the ab initio (CPA-EMTO) result of the important role of the second atomic layer to the surface is not reproducible from the large-scale Monte Carlo molecular dynamics (MCMD) simulation. On the other hand, for the nominal concentration of Cr larger than 10 at. % the MCMD simulations show the precipitation of Cr into isolated pockets in bulk Fe-Cr and the existence of the upper limit of the solubility of Cr into Fe layers in Fe/Cr layer systems. For high Cr concentration alloys the performed spectroscopic measurements support the MCMD simulations. Hard x-ray photoelectron spectroscopy and Auger electron spectroscopy investigations were carried out to explore Cr segregation and precipitation in the Fe/Cr double layer and Fe0.95Cr0.05 and Fe0.85Cr0.15 alloys. Initial oxidation of Fe-Cr was investigated experimentally at 10(-8) Torr pressure of the spectrometers showing intense Cr2O3 signal. Cr segregation and the formation of Cr-rich precipitates were traced by analyzing the experimental atomic concentrations and chemical shifts with respect to annealing time, Cr content, and kinetic energy of the exited electron.
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| 12. |
- Laukkanen, P, et al.
(författare)
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Electronic and structural properties of GaAs(100)(2x4) and InAs(100)(2x4) surfaces studied by core-level photoemission and scanning tunneling microscopy
- 2005
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Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 72:4
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Tidskriftsartikel (refereegranskat)abstract
- Electronic and structural properties of GaAs(100)(2x4), InAs(100)(2x4), and Sb/InAs(100)(2x4) reconstructed surfaces have been studied by synchrotron-radiation photoelectron spectroscopy and scanning tunneling microscopy (STM). Based on the difference spectrum of As 3d core-level spectra of III-As(100)(2x4), measured in different surface-sensitivity conditions, as well as the line shape of the As 3d emission from the Sb-induced (2x4) surface, we give evidence that the As 3d spectra of GaAs(100)(2x4) and InAs(100)(2x4) consist of two surface-core-level-shifted components. One of them is shifted about 0.2 eV to the lower kinetic energy from the bulk component. On the basis of the relative component intensities, this surface-shifted As 3d component is assigned to the emission from the first-layer As dimers in the established model of the (2x4) surface. The other component, shifted about 0.3 eV to the higher kinetic energy, is connected to the third-layer As-dimer site. The comparison of the core-level results between GaAs(100)(2x4) and InAs(100)(2x4) suggests that the alpha 2 phase, which has one As dimer in both the first and third atomic layers per unit cell, exists on GaAs(100)(2x4), similarly to the case of InAs(100)(2x4), as predicted in theory but not observed to date. Furthermore, the STM observation of the GaAs(100)(2x4)alpha 2 phase is reported.
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| 13. |
- Norrbo, Isabella, et al.
(författare)
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Mechanisms of Tenebrescence and Persistent Luminescence in Synthetic Hackmanite Na8Al6Si6O24(Cl,S)(2)
- 2016
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 8:18, s. 11592-11602
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic hackmanites, Na8Al6Si6O24(Cl,S)(2), showing efficient purple tenebrescence and blue/white persistent luminescence were studied using different spectroscopic techniques to obtain a quantified view on the storage and release of optical energy in these materials. The persistent luminescence emitter was identified as impurity Ti3+ originating from the precursor materials used in the synthesis, and the energy storage for persistent luminescence was postulated to take place in oxygen vacancies within the aluminosilicate framework. Tenebrescence, on the other hand, was observed to function within the Na-4(Cl,S) entities located in the cavities of the aluminosilicate framework. The mechanism of persistent luminescence and tenebrescence in hackmanite is presented for the first time.
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| 14. |
- Oksa, L, et al.
(författare)
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Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with no well-established prognostic biomarkers. We examined the expression of protein arginine methyltransferases across hematological malignancies and discovered high levels of PRMT7 mRNA in T-ALL, particularly in the mature subtypes of T-ALL. The genetic deletion of PRMT7 by CRISPR-Cas9 reduced the colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with the RNA and DNA processing and the T-ALL pathogenesis. Among them was RUNX1, whose target gene expression was consequently deregulated. These results suggest that PRMT7 plays an active role in the pathogenesis of T-ALL.
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| 15. |
- Pulakka, H., et al.
(författare)
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Analysis of the voice source in different phonation types : Simultaneous high-speed imaging of the vocal fold vibration and glottal inverse filtering
- 2004
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Ingår i: 8th International Conference on Spoken Language Processing, ICSLP 2004. - : International Speech Communication Association. ; , s. 1121-1124
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Konferensbidrag (refereegranskat)abstract
- Glottal flow waveforms estimated by inverse filtering acoustic speech pressure signals were compared to glottal area functions obtained by digital high-speed imaging of the vocal fold vibration. Speech data consisted of breathy, normal and pressed phonations produced by two male and one female subjects. The results yield both qualitative and quantitative information about the relationship between the glottal flow and the corresponding area function. It was shown, for example, that a distinct knee in the glottal flow waveform in the opening phase corresponds to the abrupt opening of the vocal folds in normal and pressed phonation. In addition, the obtained quantitative data corroborates known theoretical considerations according to which the shape of the glottal flow is more asymmetric than the corresponding area function.
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| 16. |
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