| 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. |
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| 3. |
- 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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| 4. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 5. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 6. |
- Baldi, R. D., et al.
(författare)
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LeMMINGs - II. The e-MERLIN legacy survey of nearby galaxies. The deepest radio view of the Palomar sample on parsec scale
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 500:4, s. 4749-4767
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Tidskriftsartikel (refereegranskat)abstract
- We present the second data release of high-resolution (≤0.2 arcsec) 1.5-GHz radio images of 177 nearby galaxies from the Palomar sample, observed with the e-MERLIN array, as part of the Legacy e-MERLIN Multi-band Imaging of Nearby Galaxies Sample (LeMMINGs) survey. Together with the 103 targets of the first LeMMINGs data release, this represents a complete sample of 280 local active (LINER and Seyfert) and inactive galaxies (H ii galaxies and absorption line galaxies, ALG). This large program is the deepest radio survey of the local Universe, ≳1017.6 W Hz-1, regardless of the host and nuclear type: we detect radio emission ≳0.25 mJy beam-1 for 125/280 galaxies (44.6 per cent) with sizes of typically ≲100 pc. Of those 125, 106 targets show a core which coincides within 1.2 arcsec with the optical nucleus. Although we observed mostly cores, around one third of the detected galaxies features jetted morphologies. The detected radio core luminosities of the sample range between ∼1034 and 1040 erg s-1. LINERs and Seyferts are the most luminous sources, whereas H ii galaxies are the least. LINERs show FR I-like core-brightened radio structures while Seyferts reveal the highest fraction of symmetric morphologies. The majority of H ii galaxies have single radio core or complex extended structures, which probably conceal a nuclear starburst and/or a weak active nucleus (seven of them show clear jets). ALGs, which are typically found in evolved ellipticals, although the least numerous, exhibit on average the most luminous radio structures, similar to LINERs.
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| 7. |
- Baldi, R. D., et al.
(författare)
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LeMMINGs III. The e-MERLIN legacy survey of the Palomar sample: Exploring the origin of nuclear radio emission in active and inactive galaxies through the [O iii] - Radio connection
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 508:2, s. 2019-2038
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Tidskriftsartikel (refereegranskat)abstract
- What determines the nuclear radio emission in local galaxies? To address this question, we combine optical [O iii] line emission, robust black hole (BH) mass estimates, and high-resolution e-MERLIN 1.5-GHz data, from the LeMMINGs survey, of a statistically complete sample of 280 nearby optically active (LINER and Seyfert) and inactive [H ii and absorption line galaxies (ALGs)] galaxies. Using [O iii] luminosity (L[O III]) as a proxy for the accretion power, local galaxies follow distinct sequences in the optical-radio planes of BH activity, which suggest different origins of the nuclear radio emission for the optical classes. The 1.5-GHz radio luminosity of their parsec-scale cores (Lcore) is found to scale with BH mass (MBH) and [O iii] luminosity. Below MBH ∼106.5 M⊙, stellar processes from non-jetted H ii galaxies dominate with Lcore ∝ MBH0.61 ± 0.33 and Lcore ∝ L[O III]0.79 ± 0.30. Above MBH ∼106.5 M⊙, accretion-driven processes dominate with Lcore ∝ MBH1.5-1.65 and Lcore ∝ L[O III]0.99-1.31 for active galaxies: radio-quiet/loud LINERs, Seyferts, and jetted H ii galaxies always display (although low) signatures of radio-emitting BH activity, with L1.5 GHz ≳ 1019.8 W Hz-1 and MBH ≳ 107 M⊙, on a broad range of Eddington-scaled accretion rates (m). Radio-quiet and radio-loud LINERs are powered by low-m discs launching sub-relativistic and relativistic jets, respectively. Low-power slow jets and disc/corona winds from moderately high to high-m discs account for the compact and edge-brightened jets of Seyferts, respectively. Jetted H ii galaxies may host weakly active BHs. Fuel-starved BHs and recurrent activity account for ALG properties. In conclusion, specific accretion-ejection states of active BHs determine the radio production and the optical classification of local active galaxies.
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| 8. |
- Bower, K. N., et al.
(författare)
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ACE-2 HILLCLOUD. An overview of the ACE-2 ground-based cloud experiment
- 2000
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Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - : Stockholm University Press. - 0280-6509. ; 52:2, s. 750-778
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Tidskriftsartikel (refereegranskat)abstract
- The ACE-2 HILLCLOUD experiment was carried out on the island of Tenerife in June-July 1997 to investigate the interaction of the boundary layer aerosol with a hill cap cloud forming over a ridge to the north-east of the island. The cloud was used as a natural flow through reactor to investigate the dependence of the cloud microphysics and chemistry on the characteristics of the aerosols and trace gases entering cloud, and to simultaneously study the influence of the physical and chemical processes occurring within the cloud on the size distribution, chemical and hygroscopic properties of the aerosol exiting cloud. 5 major ground base sites were used, measuring trace gases and aerosols upwind and downwind of the cloud, and cloud microphysics and chemistry and interstitial aerosol and gases within the cloud on the hill. 8 intensive measurement periods or runs were undertaken during cloud events, (nocturnally for seven of the eight runs) and were carried out in a wide range of airmass conditions from clean maritime to polluted continental. Polluted air was characterised by higher than average concentrations of ozone (> 50 ppbv), fine and accumulation mode aerosols (> 3000 and > 1500 cm -3 , respectively) and higher aerosol mass loadings. Cloud droplet number concentrations N, increased from 50 cm -3 in background maritime air to > 2500 cm -3 in aged polluted continental air, a concentration much higher than had previously been detected. Surprisingly, N was seen to vary almost linearly with aerosol number across this range. The droplet aerosol analyser (DAA) measured higher droplet numbers than the corrected forward scattering spectrometer probe (FSSP) in the most polluted air, but at other times there was good agreement (FSSP = 0.95 DAA with an r 2 = 0.89 for N < 1200 cm -3 ). Background ammonia gas concentrations were around 0.3 ppbv even in air originating over the ocean, another unexpected but important result for the region. NO 2 was present in background concentrations of typically 15 pptv to 100 pptv and NO 3 . (the nitrate radical) was observed at night throughout. Calculations suggest NO 3 . losses were mainly by reaction with DMS to produce nitric acid. Low concentrations of SO 2 (~30 pptv), HNO 3 and HCl were always present. HNO 3 concentrations were higher in polluted episodes and calculations implied that these exceeded those which could be accounted for by NO 2 oxidation. It is presumed that nitric and hydrochloric acids were present as a result of outgassing from aerosol, the HNO 3 from nitrate rich aerosol transported into the region from upwind of Tenerife, and HCl from sea salt aerosol newly formed at the sea surface. The oxidants hydrogen peroxide and ozone were abundant (i.e., were well in excess over SO 2 throughout the experiment). Occasions of significant aerosol growth following cloud processing were observed, particularly in cleaner cases. Observations and modelling suggested this was due mainly to the take up of nitric acid, hydrochloric acid and ammonia by the smallest activated aerosol particles. On a few occasions a small contribution was made by the in-cloud oxidation of S(IV). The implications of these results from HILLCLOUD for the climatologically more important stratocumulus Marine Boundary Layer (MBL) clouds are considered.
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| 9. |
- Baldi, R. D., et al.
(författare)
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LeMMINGs - I. The eMERLIN legacy survey of nearby galaxies. 1.5-GHz parsec-scale radio structures and cores
- 2018
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 476:3, s. 3478-3522
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Tidskriftsartikel (refereegranskat)abstract
- We present the first data release of high-resolution (≤0.2 arcsec) 1.5-GHz radio images of 103 nearby galaxies from the Palomar sample, observed with the eMERLIN array, as part of the LeMMINGs survey. This sample includes galaxies which are active (low-ionization nuclear emission-line regions [LINER] and Seyfert) and quiescent (H II galaxies and absorption line galaxies, ALGs), which are reclassified based upon revised emission-line diagrams.We detect radio emission ≳0.2 mJy for 47/103 galaxies (22/34 for LINERS, 4/4 for Seyferts, 16/51 for HII galaxies, and 5/14 for ALGs) with radio sizes typically of ≲100 pc. We identify the radio core position within the radio structures for 41 sources. Half of the sample shows jetted morphologies. The remaining half shows single radio cores or complex morphologies. LINERs show radio structures more core-brightened than Seyferts. Radio luminosities of the sample range from 1032to 1040erg s-1: LINERs and HII galaxies show the highest and lowest radio powers, respectively, while ALGs and Seyferts have intermediate luminosities. We find that radio core luminosities correlate with black hole (BH) mass down to ~107M⊙, but a break emerges at lower masses. Using [OIII] line luminosity as a proxy for the accretion luminosity, active nuclei and jetted HII galaxies follow an optical Fundamental Plane of BH activity, suggesting a common disc-jet relationship. In conclusion, LINER nuclei are the scaled-down version of FR I radio galaxies; Seyferts show less collimated jets; HII galaxies may host weak active BHs and/or nuclear star-forming cores; and recurrent BH activity may account for ALG properties.
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| 10. |
- Ginsburg, A., et al.
(författare)
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Dense gas in the Galactic central molecular zone is warm and heated by turbulence
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 586, s. Art nr A50-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Galactic center is the closest region where we can study star formation under extreme physical conditions like those in high-redshift galaxies. Aims. We measure the temperature of the dense gas in the central molecular zone (CMZ) and examine what drives it. Methods. We mapped the inner 300 pc of the CMZ in the temperature-sensitive J = 3-2 para-formaldehyde (p-H2CO) transitions. We used the 3(2,1)-2(2,0)/3(0,3)-2(0,2) line ratio to determine the gas temperature in n similar to 10(4) - 10(5) cm(-3) gas. We have produced temperature maps and cubes with 30 0 0 and 1 km s(-1) resolution and published all data in FITS form. Results. Dense gas temperatures in the Galactic center range from similar to 60 K to > 100 K in selected regions. The highest gas temperatures T-G > 100 K are observed around the Sgr B2 cores, in the extended Sgr B2 cloud, the 20 km s(-1) and 50 km s(-1) clouds, and in "The Brick" (G0.253 + 0.016). We infer an upper limit on the cosmic ray ionization rate zeta(CR)
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