| 1. |
- Sliz, E., et al.
(author)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)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. |
- Wiedensohler, A., et al.
(author)
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Mobility particle size spectrometers: harmonization of technical standards and data structure to facilitate high quality long-term observations of atmospheric particle number size distributions
- 2012
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In: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 5:3, s. 657-685
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Journal article (peer-reviewed)abstract
- Mobility particle size spectrometers often referred to as DMPS (Differential Mobility Particle Sizers) or SMPS (Scanning Mobility Particle Sizers) have found a wide range of applications in atmospheric aerosol research. However, comparability of measurements conducted world-wide is hampered by lack of generally accepted technical standards and guidelines with respect to the instrumental set-up, measurement mode, data evaluation as well as quality control. Technical standards were developed for a minimum requirement of mobility size spectrometry to perform long-term atmospheric aerosol measurements. Technical recommendations include continuous monitoring of flow rates, temperature, pressure, and relative humidity for the sheath and sample air in the differential mobility analyzer. We compared commercial and custom-made inversion routines to calculate the particle number size distributions from the measured electrical mobility distribution. All inversion routines are comparable within few per cent uncertainty for a given set of raw data. Furthermore, this work summarizes the results from several instrument intercomparison workshops conducted within the European infrastructure project EUSAAR (European Supersites for Atmospheric Aerosol Research) and ACTRIS (Aerosols, Clouds, and Trace gases Research InfraStructure Network) to determine present uncertainties especially of custom-built mobility particle size spectrometers. Under controlled laboratory conditions, the particle number size distributions from 20 to 200 nm determined by mobility particle size spectrometers of different design are within an uncertainty range of around +/- 10% after correcting internal particle losses, while below and above this size range the discrepancies increased. For particles larger than 200 nm, the uncertainty range increased to 30%, which could not be explained. The network reference mobility spectrometers with identical design agreed within +/- 4% in the peak particle number concentration when all settings were done carefully. The consistency of these reference instruments to the total particle number concentration was demonstrated to be less than 5%. Additionally, a new data structure for particle number size distributions was introduced to store and disseminate the data at EMEP (European Monitoring and Evaluation Program). This structure contains three levels: raw data, processed data, and final particle size distributions. Importantly, we recommend reporting raw measurements including all relevant instrument parameters as well as a complete documentation on all data transformation and correction steps. These technical and data structure standards aim to enhance the quality of long-term size distribution measurements, their comparability between different networks and sites, and their transparency and traceability back to raw data.
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| 3. |
- Estrada, Karol, et al.
(author)
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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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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Journal article (peer-reviewed)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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| 4. |
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| 5. |
- Kurki, MI, et al.
(author)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Journal article (peer-reviewed)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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| 6. |
- van der Werf, P.P., et al.
(author)
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Black hole accretion and star formation as drivers of gas excitation and chemistry in Markarian 231
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L42
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Journal article (peer-reviewed)abstract
- We present a full high resolution SPIRE FTS spectrum of the nearby ultraluminous infrared galaxy Mrk 231. In total 25 lines are detected, including CO J = 5-4 through J = 13-12, 7 rotational lines of H2O, 3 of OH+ and one line each of H2O+, CH+, and HF. We find that the excitation of the CO rotational levels up to J = 8 can be accounted for by UV radiation from star formation. However, the approximately flat luminosity distribution of the CO lines over the rotational ladder above J = 8 requires the presence of a separate source of excitation for the highest CO lines. We explore X-ray heating by the accreting supermassive black hole in Mrk 231 as a source of excitation for these lines, and find that it can reproduce the observed luminosities. We also consider a model with dense gas in a strong UV radiation field to produce the highest CO lines, but find that this model strongly overpredicts the hot dust mass in Mrk 231. Our favoured model consists of a star forming disk of radius 560 pc, containing clumps of dense gas exposed to strong UV radiation, dominating the emission of CO lines up to J = 8. X-rays from the accreting supermassive black hole in Mrk 231 dominate the excitation and chemistry of the inner disk out to a radius of 160 pc, consistent with the X-ray power of the AGN in Mrk 231. The extraordinary luminosity of the OH+ and H2O+ lines reveals the signature of X-ray driven excitation and chemistry in this region.
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| 7. |
- Asmi, A., et al.
(author)
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Aerosol decadal trends - Part 2: In-situ aerosol particle number concentrations at GAW and ACTRIS stations
- 2013
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 13:2, s. 895-916
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Journal article (peer-reviewed)abstract
- We have analysed the trends of total aerosol particle number concentrations (N) measured at long-term measurement stations involved either in the Global Atmosphere Watch (GAW) and/or EU infrastructure project ACTRIS. The sites are located in Europe, North America, Antarctica, and on Pacific Ocean islands. The majority of the sites showed clear decreasing trends both in the full-length time series, and in the intra-site comparison period of 2001-2010, especially during the winter months. Several potential driving processes for the observed trends were studied, and even though there are some similarities between N trends and air temperature changes, the most likely cause of many northern hemisphere trends was found to be decreases in the anthropogenic emissions of primary particles, SO2 or some co-emitted species. We could not find a consistent agreement between the trends of N and particle optical properties in the few stations with long time series of all of these properties. The trends of N and the proxies for cloud condensation nuclei (CCN) were generally consistent in the few European stations where the measurements were available. This work provides a useful comparison analysis for modelling studies of trends in aerosol number concentrations.
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| 8. |
- Asmi, A., et al.
(author)
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Number size distributions and seasonality of submicron particles in = rope 2008-2009
- 2011
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:11, s. 5505-5538
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Journal article (peer-reviewed)abstract
- Two years of harmonized aerosol number size distribution data from 24 = ropean field monitoring sites have been analysed. The results give a = mprehensive overview of the European near surface aerosol particle = mber concentrations and number size distributions between 30 and 500 = of dry particle diameter. Spatial and temporal distribution of = rosols in the particle sizes most important for climate applications = e presented. We also analyse the annual, weekly and diurnal cycles of = e aerosol number concentrations, provide log-normal fitting parameters = r median number size distributions, and give guidance notes for data = ers. Emphasis is placed on the usability of results within the aerosol = delling community.
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| 9. |
- Beddows, D. C. S., et al.
(author)
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Variations in tropospheric submicron particle size distributions across the European continent 2008-2009
- 2014
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:8, s. 4327-4348
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Journal article (peer-reviewed)abstract
- Cluster analysis of particle number size distributions from background sites across Europe is presented. This generated a total of nine clusters of particle size distributions which could be further combined into two main groups, namely: a south-to-north category (four clusters) and a west-to-east category (five clusters). The first group was identified as most frequently being detected inside and around northern Germany and neighbouring countries, showing clear evidence of local afternoon nucleation and growth events that could be linked to movement of air masses from south to north arriving ultimately at the Arctic contributing to Arctic haze. The second group of particle size spectra proved to have narrower size distributions and collectively showed a dependence of modal diameter upon the longitude of the site (west to east) at which they were most frequently detected. These clusters indicated regional nucleation (at the coastal sites) growing to larger modes further inland. The apparent growth rate of the modal diameter was around 0.6-0.9 nm h(-1). Four specific air mass back-trajectories were successively taken as case studies to examine in real time the evolution of aerosol size distributions across Europe. While aerosol growth processes can be observed as aerosol traverses Europe, the processes are often obscured by the addition of aerosol by emissions en route. This study revealed that some of the 24 stations exhibit more complex behaviour than others, especially when impacted by local sources or a variety of different air masses. Overall, the aerosol size distribution clustering analysis greatly simplifies the complex data set and allows a description of aerosol aging processes, which reflects the longer-term average development of particle number size distributions as air masses advect across Europe.
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| 10. |
- Gonzalez-Alfonso, E., et al.
(author)
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Herschel observations of water vapour in Markarian 231
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L43
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Journal article (peer-reviewed)abstract
- The Ultra luminous infrared galaxy (ULIRG) Mrk 231 reveals up to seven rotational lines of water (H2O) in emission, including a very high-lying (Eupper = 640 K) line detected at a 4 sigma level, within the Herschel/SPIRE wavelength range (190
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