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- 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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| 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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| 10. |
- Taskinen, M. R., et al.
(författare)
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Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations
- 2022
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 7:19
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Apolipoprotein C-III (apoC-III) is a regulator of triglyceride (TG) metabolism, and due to its association with risk of cardiovascular disease, is an emergent target for pharmacological intervention. The impact of substantially lowering apoC-III on lipoprotein metabolism is not clear.METHODS. We investigated the kinetics of apolipoproteins B48 and B100 (apoB48 and apoB100) in chylomicrons, VLDL1, VLDL2, IDL, and LDL in patients heterozygous for a loss-of-function (LOF) mutation in the APOC3 gene. Studies were conducted in the postprandial state to provide a more comprehensive view of the influence of this protein on TG transport.RESULTS. Compared with non-LOF variant participants, a genetically determined decrease in apoC-III resulted in marked acceleration of lipolysis of TG-rich lipoproteins (TRLs), increased removal of VLDL remnants from the bloodstream, and substantial decrease in circulating levels of VLDL1, VLDL2, and IDL particles. Production rates for apoB48-containing chylomicrons and apoB100-containing VLDL1 and VLDL2 were not different between LOF carriers and noncarriers. Likewise, the rate of production of LDL was not affected by the lower apoC-III level, nor were the concentration and clearance rate of LDL-apoB100.CONCLUSION. These findings indicate that apoC-III lowering will have a marked effect on TRL and remnant metabolism, with possibly significant consequences for cardiovascular disease prevention. TRIAL REGISTRATION. ClinicalTrials.gov NCT04209816 and NCT01445730.
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| 11. |
- Jeglinsky, I, et al.
(författare)
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Evidence on physiotherapeutic interventions for adults with cerebral palsy is sparse. A systematic review
- 2010
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Ingår i: Clinical rehabilitation. - : SAGE Publications. - 1477-0873 .- 0269-2155. ; 24:9, s. 771-788
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To identify evidence evaluating the effectiveness of physiotherapy in adolescents (>16 years of age) and adults with cerebral palsy. Data sources: Systematic literature search from the earliest available time until March 2009. Additional studies were identified through reference and citation tracking. Review methods: Two reviewers independently agreed on eligibility, methodological quality and quality of evidence assessment. Standard methods were used for quality assessments. Results: Included were 13 studies, two of which were randomized controlled trials. No article met the criteria for high methodological quality. Evidence of moderate quality was found on gait after strength training. Evidence of low quality was found on balance after strength training and workstation interventions. Low-quality evidence was also found on functionality after strength training in four studies evaluating gross motor capacity. There was very low-quality evidence on increased muscle strength and in outcome measures used to evaluate range of motion. Conclusion: Evidence for the effect of physiotherapy on adolescents and adults with cerebral palsy is sparse, and therefore there is an urgent need for well-designed physiotherapeutic trials for these people.
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| 12. |
- Ramo, Cristina, et al.
(författare)
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Latitudinal-Related Variation in Wintering Population Trends of Greylag Geese (Anser Anser) along the Atlantic Flyway: A Response to Climate Change?
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- The unusually high quality of census data for large waterbirds in Europe facilitates the study of how population change varies across a broad geographical range and relates to global change. The wintering population of the greylag goose Anser anser in the Atlantic flyway spanning between Sweden and Spain has increased from 120 000 to 610 000 individuals over the past three decades, and expanded its wintering range northwards. Although population sizes recorded in January have increased in all seven countries in the wintering range, we found a pronounced northwards latitudinal effect in which the rate of increase is higher at greater latitudes, causing a constant shift in the centre of gravity for the spatial distribution of wintering geese. Local winter temperatures have a strong influence on goose numbers but in a manner that is also dependent on latitude, with the partial effect of temperature (while controlling for the increasing population trend between years) being negative at the south end and positive at the north end of the flyway. Contrary to assumptions in the literature, the expansion of crops exploited by greylag geese has made little contribution to the increases in population size. Only in one case (expansion of winter cereals in Denmark) did we find evidence of an effect of changing land use. The expanding and shifting greylag population is likely to have increasing impacts on habitats in northern Europe during the course of this century.
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| 13. |
- Ramo, D. Munoz, et al.
(författare)
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Oxygen vacancies in cubic ZrO2 nanocrystals studied by an ab initio embedded cluster method
- 2008
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 78:23, s. 235432-
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Tidskriftsartikel (refereegranskat)abstract
- We have developed an embedded cluster method for the calculation of the electronic structure and properties of point defects in cubic ZrO2 nanocrystallites. The accuracy of the method is tested through a detailed comparison of the atomic and electronic structures of the perfect lattice and defect properties with the results of periodic calculations. The optical absorption and magnetic properties of oxygen vacancies with charge states ranging from +2 parallel to e parallel to to -2 parallel to e parallel to are calculated. Furthermore, the method can be used to study the magnetic, optical, photoluminescence, chemical, and other properties of pure and doped ZrO2 powders and their mixtures with other materials.
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