| 31. |
- Fu, Yi-Ping, et al.
(författare)
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The 19q12 Bladder Cancer GWAS Signal : Association with Cyclin E Function and Aggressive Disease
- 2014
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:20, s. 5808-5818
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Tidskriftsartikel (refereegranskat)abstract
- A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) >= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P-trend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
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| 32. |
- Gaccioli, Francesca, et al.
(författare)
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Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia
- 2020
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Ingår i: Nature Microbiology. - : Springer Nature. - 2058-5276. ; 5:7, s. 901-908
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Tidskriftsartikel (refereegranskat)abstract
- Pre-eclampsia (typically characterized by new-onset hypertension and proteinuria in the second half of pregnancy) represents a major determinant of the global burden of disease1,2. Its pathophysiology involves placental dysfunction, but the mechanism is unclear. Viral infection can cause organ dysfunction, but its role in placentally related disorders of human pregnancy is unknown3. We addressed this using RNA sequencing metagenomics4-6 of placental samples from normal and complicated pregnancies. Here, we show that human herpesvirus 6 (HHV-6, A or B) RNA was detected in 6.1% of cases of pre-eclampsia and 2.2% of other pregnancies. Fetal genotyping demonstrated that 70% of samples with HHV-6 RNA in the placenta exhibited inherited, chromosomally integrated HHV-6 (iciHHV-6). We genotyped 467 pre-eclampsia cases and 3,854 controls and found an excess of iciHHV-6 in the cases (odds ratio of 2.8, 95% confidence intervals of 1.4-5.6, P = 0.008). We validated this finding by comparing iciHHV-6 in a further 740 cases with controls from large-scale population studies (odds ratio of 2.5, 95% confidence intervals of 1.4-4.4, P = 0.0013). We conclude that iciHHV-6 results in the transcription of viral RNA in the human placenta and predisposes the mother to pre-eclampsia.
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| 33. |
- Hosseinzadeh, Griffin, et al.
(författare)
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Photometric Classification of 2315 Pan-STARRS1 Supernovae with Superphot
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:2
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Tidskriftsartikel (refereegranskat)abstract
- The classification of supernovae (SNe) and its impact on our understanding of explosion physics and progenitors have traditionally been based on the presence or absence of certain spectral features. However, current and upcoming wide-field time-domain surveys have increased the transient discovery rate far beyond our capacity to obtain even a single spectrum of each new event. We must therefore rely heavily on photometric classification-connecting SN light curves back to their spectroscopically defined classes. Here, we present Superphot, an open-source Python implementation of the machine-learning classification algorithm of Villar et al., and apply it to 2315 previously unclassified transients from the Pan-STARRS1 Medium Deep Survey for which we obtained spectroscopic host-galaxy redshifts. Our classifier achieves an overall accuracy of 82%, with completenesses and purities of >80% for the best classes (SNe Ia and superluminous SNe). For the worst performing SN class (SNe Ibc), the completeness and purity fall to 37% and 21%, respectively. Our classifier provides 1257 newly classified SNe Ia, 521 SNe II, 298 SNe Ibc, 181 SNe IIn, and 58 SLSNe. These are among the largest uniformly observed samples of SNe available in the literature and will enable a wide range of statistical studies of each class.
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| 34. |
- Iacoangeli, Alfredo, et al.
(författare)
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SCFD1 expression quantitative trait loci in amyotrophic lateral sclerosis are differentially expressed
- 2021
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Ingår i: Brain Communications. - : Oxford University Press. - 2632-1297. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Evidence indicates that common variants found in genome-wide association studies increase risk of disease through gene regulation via expression Quantitative Trait Loci. Using multiple genome-wide methods, we examined if Single Nucleotide Polymorphisms increase risk of Amyotrophic Lateral Sclerosis through expression Quantitative Trait Loci, and whether expression Quantitative Trait Loci expression is consistent across people who had Amyotrophic Lateral Sclerosis and those who did not. In combining public expression Quantitative Trait Loci data with Amyotrophic Lateral Sclerosis genome-wide association studies, we used Summary-data-based Mendelian Randomization to confirm that SCFD1 was the only gene that was genome-wide significant in mediating Amyotrophic Lateral Sderosis risk via expression Quantitative Trait Loci (Summary-data-based Mendelian Randomization beta = 0.20, standard error = 0.04, P-value = 4.29 x 10(-6)). Using post-mortem motor cortex, we tested whether expression Quantitative Trait Loci showed significant differences in expression between Amyotrophic Lateral Sclerosis (n= 76) and controls (n= 25), genome-wide. Of 20 757 genes analysed, the two most sign ificant expression Quantitative Trait Loci to show differential in expression between Amyotrophic Lateral Sclerosis and controls involve two known Amyotrophic Lateral Sclerosis genes (SCFD1 and VCP). Cis-acting SCFD1 expression Quantitative Trait Loci downstream of the gene showed significant differences in expression between Amyotrophic Lateral Sclerosis and controls (top expression Quantitative Trait Lod beta = 0.34, standard error = 0.063, P-value = 4.54 x 10(-7)). These SCFD1 expression Quantitative Trait Loci also significantly modified Amyotrophic Lateral Sclerosis survival (number of samples = 4265, hazard ratio = 1.11, 95% confidence interval = 1.05-1.17, P-value = 2.06 x 10(-4)) and act as an Amyotrophic Lateral Sclerosis trans-expression Quantitative Trait Loci hotspot for a wider network of genes enriched for SCFD1 function and Amyotrophic Lateral Sderosis pathways. Using gene-set analyses, we found the genes that correlate with this trans-expression Quantitative Trait Loci hotspot significantly increase risk of Amyotrophic La teral Sderosis (beta = 0.247, standard deviation = 0.017, P= 0.001) and schizophrenia (beta = 0.263, standard deviation = 0.008, P-value 1.18 x 10(-5)), a disease that genetically correlates with Amyotrophic Lateral Sclerosis. In summary, SCFD1 expression Quantitative Trait Lod are a major factor in Amyotrophic Lateral Sderosis, not only influencing disease risk but are differentially expressed in post-mortem Amyotrophic Lateral Sclerosis. SCFD1 expression Quantitative Trait Loci show distinct expression profiles in Amyotrophic Lateral Sclerosis that correlate with a wider network of genes that also confer risk of the disease and modify the disease's duration.
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| 35. |
- Jang, Seon-Kyeong, et al.
(författare)
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Rare genetic variants explain missing heritability in smoking.
- 2022
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Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 6:11, s. 1577-1586
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.
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| 36. |
- Jones, Ashley, 1977, et al.
(författare)
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Analysis of HCl and ClO time series in the upper stratosphere using satellite data sets
- 2011
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:11, s. 5321-5333
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Tidskriftsartikel (refereegranskat)abstract
- Previous analyses of satellite and ground-based measurements of hydrogen chloride (HCl) and chlorine monoxide (ClO) have suggested that total inorganic chlorine in the upper stratosphere is on the decline. We create HCl and ClO time series using satellite data sets extended to November 2008, so that an update can be made on the long term evolution of these two species. We use the HALogen Occultation Experiment (HALOE) and the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) data for the HCl analysis, and the Odin Sub-Millimetre Radiometer (SMR) and the Aura Microwave Limb Sounder (Aura-MLS) measurements for the study of ClO. Altitudes between 35 and 45 km and two mid-latitude bands: 30° S–50° S and 30° N–50° N, for HCl, and 20° S–20° N for ClO and HCl are studied. ACE-FTS and HALOE HCl anomaly time series (with QBO and seasonal contributions removed) are combined to produce all instrument average time series, which show HCl to be reducing from peak 1997 values at a linear estimated rate of −5.1 % decade−1 in the Northern Hemisphere and −5.2 % decade−1 in the Southern Hemisphere, while the tropics show a linear trend of −5.8 % per decade (although we do not remove the QBO contribution there due to sparse data). Trend values are significantly different from a zero trend at the 2 sigma level. ClO is decreasing in the tropics by −7.1 % ± 7.8 % decade−1 based on measurements made from December 2001 to November 2008. The statistically significant downward trend found in HCl after 1997 and the apparent downward ClO trend since 2001 (although not statistically significant) confirm how effective the 1987 Montreal protocol objectives and its amendments have been in reducing the total amount of inorganic chlorine.
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| 37. |
- Jones, Ashley, 1977, et al.
(författare)
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Analyzing the applications of an assimilation model as a method for validation of satellite data
- 2007
-
Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 112:D17101
-
Tidskriftsartikel (refereegranskat)abstract
- An analysis was performed to illustrate that data assimilation is an appropriate method for validation of satellite measurements when very few coincidences are available between satellite measurements and balloon sondes. Results showed that the mean differences between the Isentropic Assimilation model for StratospheriC Ozone (IASCO) model ozone profiles and co-located ozone sondes shared systematic differences similar to those obtained from co-located MIPAS and ozone sonde coincidences. The spatial and temporal constraints of 12 hours and 800 km produced the optimal number of MIPAS/sonde matches for a statistical analysis. The largest residual between the IASCO/sonde mean difference and MIPAS/sonde mean difference, using these constraints, was less than 0.25 ppmv, between potential temperature levels of 425-975 K. By using the assimilation model coincidences, we also conclude that the maximum time/distance constraint sizes that can be used when obtaining matches between satellite measurements and in-situ measurements should be no more than 24 hours and a maximum of 1500-2000 km. However, local conditions such as the presence of a dynamical feature, for example the edge of the polar vortex, may of course greatly restrict these limits.
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| 38. |
- Jones, Ashley, 1977, et al.
(författare)
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Evolution of stratospheric ozone and water vapour time series studied with satellite measurements
- 2009
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 9, s. 6055-6075
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Tidskriftsartikel (refereegranskat)abstract
- The long term evolution of stratospheric ozone and water vapour has been investigated by extending satellite time series to April 2008. For ozone, we examine monthly average ozone values from various satellite data sets for nine latitude and altitude bins covering 60° S to 60° N and 20–45 km and covering the time period of 1979–2008. Data are from the Stratospheric Aerosol and Gas Experiment (SAGE I+II), the HALogen Occultation Experiment (HALOE), the Solar BackscatterUltraViolet-2 (SBUV/2) instrument, the Sub-Millimetre Radiometer (SMR), the Optical Spectrograph InfraRed Imager System (OSIRIS), and the SCanning Imaging Absorption spectroMeter for Atmospheric CHartograpY (SCIAMACHY). Monthly ozone anomalies are calculated by utilising a linear regression model, which also models the solar, quasi-biennial oscillation (QBO), and seasonal cycle contributions. Individual instrument ozone anomalies are combined producing an all instrument average. Assuming a turning point of 1997 and that the all instrument average is represented by good instrumental long term stability, the largest statistically significant ozone declines (at two sigma) from 1979–1997 are seen at the mid-latitudes between 35 and 45 km, namely −7.2%±0.9%/decade in the Northern Hemisphere and −7.1%±0.9%/in the Southern Hemisphere. Furthermore, for the period 1997 to 2008 we find that the same locations show the largest ozone recovery (+1.4% and +0.8%/decade respectively) compared to other global regions, although the estimated trend model errors indicate that the trend estimates are not significantly different from a zero trend at the 2 sigma level. An all instrument average is also constructed from water vapour anomalies during 1991–2008, using the SAGE II, HALOE, SMR, and the Microwave Limb Sounder (Aura/MLS) measurements. We report that the decrease in water vapour values after 2001 slows down around 2004–2005 in the lower tropical stratosphere (20–25 km) and has even shown signs of increasing until present. We show that a similar correlation is also seen with the temperature measured at 100 hPa during this same period.
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| 39. |
- Jones, Ashley, 1977, et al.
(författare)
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Intercomparison of Odin/SMR Ozone measurements with MIPAS and balloon sonde data
- 2007
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Ingår i: Canadian Journal of Physics. ; 85:11, s. 1111-1123
-
Tidskriftsartikel (refereegranskat)abstract
- The Sub-Millimetre Radiometer (SMR) on board Odin measures various important atmospheric species, including stratospheric ozone. In this study we compare the three versions (v1.2, v2.0 and v2.1) of level 2 Odin/SMR global stratospheric ozone data to coincident level 2 MIPAS V4.61 and balloon sonde stratospheric ozone data during 2003. The most current product from Odin/SMR (at time of writing), the v2.1, showed the smallest systematic differences when compared to coincident MIPAS and sonde data. Between 17 and 55 km, v2.1 values agreed with MIPAS within 10% (a maximum of 0.42 ppmv), while comparisons to sonde measurements showed an agreement of typically 5-10% between 22 and 35 km (less than 0.5 ppmv below 33 km). Tropical latitudes below 35 km preseneted the largest absolute systematic differences between v2.1 and sonde coincidences, where Odin/SMR was systematically lower by ~0.9 ppmv (more than 10% difference) at approximately 30 km. Comparisons concerning the previous two Odin/SMR versions showed much larger systematic differences, especially at the higher and lower stratospheric altitudes. The main conclusion here is that we suggest that v2.1 of Odin/SMR ozone data should be used for scientific studies.
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| 40. |
- Jones, Amy M., et al.
(författare)
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SDSS-IV from 2014 to 2016 : A Detailed Demographic Comparison over Three Years
- 2023
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Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280. ; 135:1054
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Tidskriftsartikel (refereegranskat)abstract
- The Sloan Digital Sky Survey (SDSS) is one of the largest international astronomy organizations. We present demographic data based on surveys of its members from 2014, 2015 and 2016, during the fourth phase of SDSS (SDSS-IV). We find about half of SDSS-IV collaboration members were based in North America, a quarter in Europe, and the remainder in Asia and Central and South America. Overall, 26%-36% are women (from 2014 to 2016), up to 2% report non-binary genders. 11%-14% report that they are racial or ethnic minorities where they live. The fraction of women drops with seniority, and is also lower among collaboration leadership. Men in SDSS-IV were more likely to report being in a leadership role, and for the role to be funded and formally recognized. SDSS-IV collaboration members are twice as likely to have a parent with a college degree, than the general population, and are ten times more likely to have a parent with a PhD. This trend is slightly enhanced for female collaboration members. Despite this, the fraction of first generation college students is significant (31%). This fraction increased among collaboration members who are racial or ethnic minorities (40%-50%), and decreased among women (15%-25%). SDSS-IV implemented many inclusive policies and established a dedicated committee, the Committee on INclusiveness in SDSS. More than 60% of the collaboration agree that the collaboration is inclusive; however, collaboration leadership more strongly agree with this than the general membership. In this paper, we explain these results in full, including the history of inclusive efforts in SDSS-IV. We conclude with a list of suggested recommendations based on our findings, which can be used to improve equity and inclusion in large astronomical collaborations, which we argue is not only moral, but will also optimize their scientific output.
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