| 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. |
- Holopainen, Päivi, et al.
(författare)
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Candidate gene region 2q33 in European families with coeliac disease.
- 2004
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Ingår i: Tissue antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 63:3, s. 212-22
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome region 2q33 harbours a cluster of genes, CTLA-4, CD28, ICOS and closely located PD-1, all related to immune activation and considered as promising candidate genes for susceptibility to coeliac disease (CD). We present here the results of a genetic linkage and association analysis of nine markers located in this gene region in a large combined European material of 796 families with CD from Finland, Sweden, Norway, UK, France and Italy. The joint analysis supports earlier findings that this susceptibility locus, assigned as CELIAC3, merits further studies. Nominally significant linkage to CD was found in 314 families including affected sib pairs. Each of the five populations showed weak associations to several marker alleles, but the analysis revealed, however, no conclusive evidence for a primary functional gene or gene variant present in the total set of families. The results suggest that the CD risk due to 2q33 gene region is complex and may involve more than one susceptibility allele, which possibly differ from other autoimmune diseases.
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| 6. |
- Lorenz, Ch, et al.
(författare)
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β Decay of 127Cd and Excited States in 127In
- 2019
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Ingår i: Physical Review C. - 2469-9985. ; 99:4
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Tidskriftsartikel (refereegranskat)abstract
- A dedicated spectroscopic study of the β decay of 127Cd was conducted at the IGISOL facility at the University of Jyväskylä. Following high-resolution mass separation in a Penning trap, β-γ-γ coincidences were used to considerably extend the decay scheme of 127In. The β-decaying 3/2+ and 11/2- states in 127Cd have been identified with the 127Cd ground state and the 283-keV isomer. Their respective half-lives have been measured to 0.45(+12-8)s and 0.36(4) s. The experimentally observed β feeding to excited states of 127In and the decay scheme of 127In are discussed in conjunction with large-scale shell-model calculations.
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| 7. |
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| 8. |
- Parr, E., et al.
(författare)
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Single-particle states and parity doublets in odd- Z Ac 221 and Pa 225 from α -decay spectroscopy
- 2022
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Ingår i: Physical Review C. - 2469-9985. ; 105:3
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Tidskriftsartikel (refereegranskat)abstract
- Low-lying states in the odd-Z isotopes Ac13289221 and Pa13491225 have been studied using α-particle and αγ-coincidence spectroscopy in the Pa225→Ac221→Fr217 decay chain. Ground-state spin and parity assignments of Iπ = 5/2- are proposed for both Ac221 and Pa225, with the odd proton occupying the ω = 5/2 orbital of the quadrupole-octupole deformed shell model in both nuclei. In Ac221, excited states in the bands based on the ω = 5/2 and ω = 3/2 orbitals have been identified, including proposed parity-doublet states. The results suggest that reflection-asymmetric deformation of the ground state persists in the odd-A members of the isotope chains down to N = 132 for Ac and N = 134 for Pa, before reaching the transitional region at N = 130.
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| 9. |
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| 10. |
- Petrache, C. M., et al.
(författare)
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Collective rotation of an oblate nucleus at very high spin
- 2019
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Ingår i: Physical Review C. - : American Physical Society (APS). - 2469-9985 .- 2469-9993. ; 99:4
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Tidskriftsartikel (refereegranskat)abstract
- A sequence of nine almost equidistant quadrupole transitions is observed in Nd137. The sequence represents an extremely regular rotational band that extends to a spin of about 75/2 and an excitation energy of ≈4.5MeV above yrast. Cranked mean-field calculations of the Nilsson-Strutinsky type suggest an oblate shape for the band. They reproduce the observed I(I+1) dependence of the rotational energy whereas predicting a pronounced decrease in the deformation, which is the hallmark of antimagnetic rotation.
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