| 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. |
- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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| 6. |
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| 7. |
- Briselet, R., et al.
(författare)
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Production cross section and decay study of Es 243 and Md 249
- 2019
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Ingår i: Physical Review C. - 2469-9985. ; 99:2
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Tidskriftsartikel (refereegranskat)abstract
- In the study of the odd-Z, even-N nuclei Es243 and Md249, performed at the University of Jyväskylä, the fusion-evaporation reactions Au197(Ca48,2n)Es243 and Tl203(Ca48,2n)Md249 have been used for the first time. Fusion-evaporation residues were selected and detected using a gas-filled separator coupled with its focal-plane spectrometer. For Es243, the recoil decay correlation analysis yielded a half-life of 24±3s and a maximum production cross section of 37±10nb. In the same way, a half-life of 26±1s, an α-branching ratio of 75±5%, and a maximum production cross section of 300±80nb were determined for Md249. The decay properties of Es245, the daughter of Md249, were also measured: an α-branching ratio of 54±7% and a half-life of 65±6s. Experimental cross sections were compared to the results of calculations performed using the kewpie2 statistical fusion-evaporation code.
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| 8. |
- Hilton, J., et al.
(författare)
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α -spectroscopy studies of the new nuclides Pt 165 and Hg 170
- 2019
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Ingår i: Physical Review C. - 2469-9985. ; 100:1
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Tidskriftsartikel (refereegranskat)abstract
- The new nuclides Pt165 and Hg170 were produced in the reactions Mo92(Kr78,5n) and Ru96(Kr78,4n) at bombarding energies of 418 MeV and 390 MeV, respectively. For Hg170 an α-particle energy of Eα=7590(30)keV and half-life of t1/2=0.08-0.04+0.40ms were deduced, while for Pt165 the corresponding values were 7272(14) keV and 0.26-0.09+0.26ms. Comparison of the reduced α-decay widths with systematics indicates that both α decays are unhindered. Although combining the measured α-decay Q values with extrapolated masses suggests that both new nuclides are unbound to two-proton emission by more than 1 MeV, their α-decay half-lives are too short for this decay mode to compete. Improved data were also obtained for Pt166,167, produced via the Ru96(Kr78,α4n) and Ru96(Kr78,α3n) reactions at bombarding energies of 390 MeV and 418 MeV.
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| 9. |
- Lewis, M. C., et al.
(författare)
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Decay of a 19(-) isomeric state in Lu-156
- 2018
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 98:2
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Tidskriftsartikel (refereegranskat)abstract
- A multiparticle spin-trap isomeric state having a half-life of 179(4) ns and lying 2601 keV above the yrast 10(+) state in Lu-156 has been discovered. The Lu-156 nuclei were produced by bombarding isotopically enriched Cd-106 targets with beams of Ni-58 ions, separated in flight using the gas-filled separator RITU and their decays were measured using the GREAT spectrometer. Analysis of the main decay path that populates yrast states observed previously suggests a spin-parity assignment of 19(-) for the isomeric state, which is consistent with isomeric states identified in the N = 85 isotones. Comparison with other decay paths in Lu-156 indicates that the [pi h(11/)(2)(-1) circle times nu h(9/2)]10(+) state at the bottom of the yrast sequence is likely to be the a-decaying isomeric state, with the [pi h(11/)(2)(-1) circle times nu f(7/2)]9(+) state lying 62 keV above it. The relative ordering of the lowest-lying 9(+) and 10(+) states is inverted in Lu-156 compared with its odd-odd isotones.
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| 10. |
- Lynge, E, et al.
(författare)
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Risk of cancer and exposure to gasoline vapors
- 1997
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Ingår i: American journal of epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 145:5, s. 449-458
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Tidskriftsartikel (refereegranskat)
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