| 1. |
- Justice, A. E., et al.
(författare)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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| 2. |
- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 3. |
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| 4. |
- Vieira-Silva, S., et al.
(författare)
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Statin therapy is associated with lower prevalence of gut microbiota dysbiosis
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 581:7808, s. 310-315
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Tidskriftsartikel (refereegranskat)abstract
- Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n=888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n=2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
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| 5. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 6. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 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
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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| 7. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 8. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 9. |
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| 10. |
- Albrechtsen, A., et al.
(författare)
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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 298-310
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Tidskriftsartikel (refereegranskat)abstract
- Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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| 11. |
- Esposito, M., et al.
(författare)
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HD 219666 b: a hot-Neptune from TESS Sector 1
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623:623
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Tidskriftsartikel (refereegranskat)abstract
- We report on the confirmation and mass determination of a transiting planet orbiting the old and inactive G7 dwarf star HD219666 (M-star = 0.92 +/- 0.03 M-circle dot, R-star = 1.03 +/- 0.03 R-circle dot, tau(star) = 10 +/- 2 Gyr). With a mass of M-b = 16.6 +/- 1.3 M-circle plus, a radius of R-b = 4.71 +/- 0.17 R-circle plus, and an orbital period of P-orb similar or equal to 6 days, HD219666 b is a new member of a rare class of exoplanets: the hot-Neptunes. The Transiting Exoplanet Survey Satellite (TESS) observed HD219666 (also known as TOI-118) in its Sector 1 and the light curve shows four transit-like events, equally spaced in time. We confirmed the planetary nature of the candidate by gathering precise radial-velocity measurements with the High Accuracy Radial velocity Planet Searcher (HARPS) at ESO 3.6 m. We used the co-added HARPS spectrum to derive the host star fundamental parameters (T-eff = 5527 +/- 65 K, log g(star) = 4.40 +/- 0.11 (cgs), [Fe/H] = 0.04 +/- 0.04 dex, log R-HK' = -5.07 +/- 0.03), as well as the abundances of many volatile and refractory elements. The host star brightness (V = 9.9) makes it suitable for further characterisation by means of in-transit spectroscopy. The determination of the planet orbital obliquity, along with the atmospheric metal-to-hydrogen content and thermal structure could provide us with important clues on the formation mechanisms of this class of objects.
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| 12. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 13. |
- Hidalgo, D., et al.
(författare)
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Three planets transiting the evolved star EPIC 249893012: a hot 8.8-Mearth super-Earth and two warm 14.7 and 10.2-Mearth sub-Neptunes
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a new planetary system with three transiting planets, one super-Earth and two sub-Neptunes, that orbit EPIC 249893012, a G8 IV-V evolved star (M⋆ = 1.05 ± 0.05 M☉, R⋆ = 1.71 ± 0.04 R☉, Teff = 5430 ± 85 K). The star is just leaving the main sequence. We combined K2 photometry with IRCS adaptive-optics imaging and HARPS, HARPS-N, and CARMENES high-precision radial velocity measurements to confirm the planetary system, determine the stellar parameters, and measure radii, masses, and densities of the three planets. With an orbital period of 3.5949-0.0007+0.0007days, a mass of 8.75-1.08+1.09 M⊕, and a radius of 1.95-0.08+0.09 R⊕, the inner planet b is compatible with nickel-iron core and a silicate mantle (ρb = 6.39-1.04+1.19 g cm-3). Planets c and d with orbital periods of 15.624-0.001+0.001 and 35.747-0.005+0.005 days, respectively, have masses and radii of 14.67-1.89+1,84 M⊕ and 3.67-0.14+0.17 R⊕ and 10.18-2.42+2.46 M⊕ and 3.94-0.12+0.13 R⊕, respectively, yielding a mean density of 1.62-0.29+0.30 and 0.91-0.23+0.25 g cm-3, respectively. The radius of planet b lies in the transition region between rocky and gaseous planets, but its density is consistent with a rocky composition. Its semimajor axis and the corresponding photoevaporation levels to which the planet has been exposed might explain its measured density today. In contrast, the densities and semimajor axes of planets c and d suggest a very thick atmosphere. The singularity of this system, which orbits a slightly evolved star that is just leaving the main sequence, makes it a good candidate for a deeper study from a dynamical point of view.
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| 14. |
- Dai, F., et al.
(författare)
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The Discovery and Mass Measurement of a New Ultra-short-period Planet: K2-131
- 2017
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 154:6, s. 226-
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a new ultra-short-period planet and summarize the properties of all such planets for which the mass and radius have been measured. The new planet, EPIC 228732031b, was discovered in K2 Campaign 10. It has a radius of 1.81-0.12+0.16 R_Earth and orbits a G dwarf with a period of 8.9 hr. Radial velocities obtained with Magellan/PFS and TNG/HARPS-N show evidence for stellar activity along with orbital motion. We determined the planetary mass using two different methods: (1) the “floating chunk offset” method, based only on changes in velocity observed on the same night; and (2) a Gaussian process regression based on both the radial velocity and photometric time series. The results are consistent and lead to a mass measurement of 6.5+/- 1.6 M_Earth and a mean density of 6.0-2.7+3.0 g cm‑3.
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| 15. |
- Luque, R., et al.
(författare)
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Detection and characterization of an ultra-dense sub-Neptunian planet orbiting the Sun-like star K2-292
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery and characterization of a new transiting planet from Campaign 17 of the Kepler extended mission K2. The planet K2-292 b is a warm sub-Neptune on a 17 day orbit around a bright (V = 9.9 mag) solar-like G3 V star with a mass and radius of M⋆ = 1.00 ± 0.03 M⊙ and R⋆ = 1.09 ± 0.03 R⊙, respectively. We modeled simultaneously the K2 photometry and CARMENES spectroscopic data and derived a radius of Rp=2.63-0.10+0.12 R⊕ and mass of Mp=24.5-4.4+4.4 M⊕, yielding a mean density of ρp=7.4-1.5+1.6 g cm-3, which makes it one of the densest sub-Neptunian planets known to date. We also detected a linear trend in the radial velocities of K2-292 (γ˙RV = -0.40-0.07+0.07 m s-1 d-1) that suggests a long-period companion with a minimum mass on the order of 33 M⊕. If confirmed, it would support a formation scenario of K2-292 b by migration caused by Kozai-Lidov oscillations.
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| 16. |
- Van Eylen, Vincent, et al.
(författare)
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Masses and compositions of three small planets orbiting the nearby M dwarf L231-32 (TOI-270) and the M dwarf radius valley
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 507:2, s. 2154-2173
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Tidskriftsartikel (refereegranskat)abstract
- We report on precise Doppler measurements of L231-32 (TOI-270), a nearby M dwarf (d = 22 pc, M = 0.39 M, R = 0.38 R), which hosts three transiting planets that were recently discovered using data from the Transiting Exoplanet Survey Satellite (TESS). The three planets are 1.2, 2.4, and 2.1 times the size of Earth and have orbital periods of 3.4, 5.7, and 11.4 d. We obtained 29 high-resolution optical spectra with the newly commissioned Echelle Spectrograph for Rocky Exoplanet and Stable Spectroscopic Observations (ESPRESSO) and 58 spectra using the High Accuracy Radial velocity Planet Searcher (HARPS). From these observations, we find the masses of the planets to be 1.58 ± 0.26, 6.15 ± 0.37, and 4.78 ± 0.43 M, respectively. The combination of radius and mass measurements suggests that the innermost planet has a rocky composition similar to that of Earth, while the outer two planets have lower densities. Thus, the inner planet and the outer planets are on opposite sides of the 'radius valley'-a region in the radius-period diagram with relatively few members-which has been interpreted as a consequence of atmospheric photoevaporation. We place these findings into the context of other small close-in planets orbiting M dwarf stars, and use support vector machines to determine the location and slope of the M dwarf (Teff < 4000 K) radius valley as a function of orbital period. We compare the location of the M dwarf radius valley to the radius valley observed for FGK stars, and find that its location is a good match to photoevaporation and core-powered mass-loss models. Finally, we show that planets below the M dwarf radius valley have compositions consistent with stripped rocky cores, whereas most planets above have a lower density consistent with the presence of a H-He atmosphere.
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| 17. |
- Gandolfi, D., et al.
(författare)
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The Transiting Multi-planet System HD15337: Two Nearly Equal-mass Planets Straddling the Radius Gap
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 876:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a super-Earth and a sub-Neptune transiting the star HD 15337 (TOI-402, TIC 120896927), a bright (V = 9) K1 dwarf observed by the Transiting Exoplanet Survey Satellite (TESS) in Sectors 3 and 4. We combine the TESS photometry with archival High Accuracy Radial velocity Planet Searcher spectra to confirm the planetary nature of the transit signals and derive the masses of the two transiting planets. With an orbital period of 4.8 days, a mass of {7.51}-1.01+1.09 {M}\oplus and a radius of 1.64 ± 0.06 R ⊕, HD 15337 b joins the growing group of short-period super-Earths known to have a rocky terrestrial composition. The sub-Neptune HD 15337 c has an orbital period of 17.2 days, a mass of {8.11}-1.69+1.82 {{{M}}}\oplus , and a radius of 2.39 ± 0.12 R ⊕, suggesting that the planet might be surrounded by a thick atmospheric envelope. The two planets have similar masses and lie on opposite sides of the radius gap, and are thus an excellent testbed for planet formation and evolution theories. Assuming that HD 15337 c hosts a hydrogen-dominated envelope, we employ a recently developed planet atmospheric evolution algorithm in a Bayesian framework to estimate the history of the high-energy (extreme ultraviolet and X-ray) emission of the host star. We find that at an age of 150 Myr, the star possessed on average between 3.7 and 127 times the high-energy luminosity of the current Sun.
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| 18. |
- Persson, Carina, 1964, et al.
(författare)
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Super-Earth of 8 Mearth in a 2.2-day orbit around the K5V star K2-216
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 618:33
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Tidskriftsartikel (refereegranskat)abstract
- Although thousands of exoplanets have been discovered to date, far fewer have been fully characterised, in particular super- Earths. The KESPRINT consortium identified K2-216 as a planetary candidate host star in the K2 space mission Campaign 8 field with a transiting super-Earth. The planet has recently been validated as well. Our aim was to confirm the detection and derive the main physical characteristics of K2-216b, including the mass. We performed a series of follow-up observations: high resolution imaging with the FastCam camera at the TCS, the Infrared Camera and Spectrograph at Subaru, and high resolution spectroscopy with HARPS (ESO, La Silla), HARPS-N (TNG), and FIES (NOT). The stellar spectra were analyzed with the SpecMatch-Emp and SME codes to derive the stellar fundamental properties. We analyzed the K2 light curve with the Pyaneti software. The radial-velocity measurements were modelled with both a Gaussian process (GP) regression and the floating chunk offset (FCO) technique to simultaneously model the planetary signal and correlated noise associated with stellar activity. Imaging confirms that K2-216 is a single star. Our analysis discloses that the star is a moderately active K5V star of mass 0.70+/-0.03 Msun and radius 0.72+/-0.03 Rsun. Planet b is found to have a radius of 1.75+0.17-0.10 Rearth and a 2.17-day orbit in agreement with previous results. We find consistent results for the planet mass from both models: 7.4+/-2.2 Mearth from the GP regression, and 8.0+/-1.6 Mearth from the FCO technique, which implies that this planet is a super-Earth. The planet parameters put planet b in the middle of, or just below, the gap of the radius distribution of small planets. The density is consistent with a rocky composition of primarily iron and magnesium silicate. In agreement with theoretical predictions, we find that the planet is a remnant core, stripped of its atmosphere, and is one of the largest planets found that has lost its atmosphere.
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| 19. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 20. |
- Korth, J., et al.
(författare)
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K2-140b and K2-180b - Characterization of a hot Jupiter and a mini-Neptune from the K2 mission
- 2019
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 482:2, s. 1807-1823
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Tidskriftsartikel (refereegranskat)abstract
- We report the independent discovery and characterization of two K2 planets: K2-180b, a mini-Neptune-sized planet in an 8.9-d orbit transiting a V = 12.6 mag, metal-poor ([Fe/H] = -0.65 ± 0.10) K2V star in K2 campaign 5; K2-140b, a transiting hot Jupiter in a 6.6-d orbit around a V = 12.6 mag G6V ([Fe/H] = + 0.10 ± 0.10) star in K2 campaign 10. Our results are based on K2 time-series photometry combined with high-spatial resolution imaging and high-precision radial velocity measurements. We present the first mass measurement of K2-180b. K2-180b has a mass of Mp = 11.3 ± 1.9 M_Earth and a radius of Rp = 2.2 ± 0.1 R_Earth, yielding a mean density of ρp = 5.6 ± 1.9 g cm-3, suggesting a rocky composition. Given its radius, K2-180b is above the region of the so-called `planetary radius gap'. K2-180b is in addition not only one of the densest mini-Neptune-sized planets, but also one of the few mini-Neptune-sized planets known to transit a metal-poor star. We also constrain the planetary and orbital parameters of K2-140b and show that, given the currently available Doppler measurements, the eccentricity is consistent with zero, contrary to the results of a previous study.
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| 21. |
- Hjorth, M., et al.
(författare)
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K2-290: A warm Jupiter and a mini-Neptune in a triple-star system
- 2019
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 484:3, s. 3522-3536
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of two transiting planets orbiting K2-290 (EPIC 249624646), a bright (V = 11.11) late F-type star residing in a triple-star system. It was observed during Campaign 15 of the K2 mission, and in order to confirm and characterize the system, follow-up spectroscopy and AO imaging were carried out using the FIES, HARPS, HARPS-N, and IRCS instruments. From AO imaging and Gaia data we identify two M-dwarf companions at a separation of 113 ± 2 and 2467+−177155 au. From radial velocities, K2 photometry, and stellar characterization of the host star, we find the inner planet to be a mini-Neptune with a radius of 3.06 ± 0.16 R and an orbital period of P = 9.2 d. The radius of the mini-Neptune suggests that the planet is located above the radius valley, and with an incident flux of F ∼ 400 F, it lies safely outside the super-Earth desert. The outer warm Jupiter has a mass of 0.774 ± 0.047 MJ and a radius of 1.006 ± 0.050 RJ, and orbits the host star every 48.4 d on an orbit with an eccentricity e < 0.241. Its mild eccentricity and mini-Neptune sibling suggest that the warm Jupiter originates from in situ formation or disc migration.
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| 22. |
- Jackson, Victoria E, et al.
(författare)
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Meta-analysis of exome array data identifies six novel genetic loci for lung function.
- 2018
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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| 23. |
- Johnson, M.C., et al.
(författare)
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K2-260 b: A hot Jupiter transiting an F star, and K2-261 b: A warm Saturn around a bright G star
- 2018
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 481:1, s. 596-612
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery and confirmation of two new transiting giant planets from the Kepler extended mission K2. K2-260 b is a hot Jupiter transiting a V = 12.7 F6V star in K2 Field 13, with a mass and radius of M = 1.39-0.06+0.05M⊙and R = 1.69 ± 0.03 R. The planet has an orbital period of P = 2.627 d, and a mass and radius of MP= 1.42-0.32+0.31MJand RP= 1.552-0.057+0.048RJ. This is the first K2 hot Jupiter with a detected secondary eclipse in the Kepler bandpass, with a depth of 71 ± 15 ppm, which we use to estimate a geometric albedo of Ag~ 0.2. We also detected a candidate stellar companion at 0.6 arcsec from K2-260; we find that it is very likely physically associated with the system, in which case it would be an M5-6V star at a projected separation of ~400 au. K2-261 b is a warm Saturn transiting a bright (V = 10.5) G7IV/V star in K2 Field 14. The host star is a metal rich ([Fe/H] = 0.36 ± 0.06), mildly evolved 1.10-0.02+0.01M⊙star with R = 1.65 ± 0.04 R. Thanks to its location near the main-sequence turn-off, we can measure a relatively precise age of 8.8-0.3+0.4Gyr. The planet has P = 11.633 d, MP= 0.223 ± 0.031 MJ, and RP= 0.850-0.022+0.026RJ, and its orbit is eccentric (e = 0.39 ± 0.15). Its brightness and relatively large transit depth make this one of the best-known warm Saturns for follow-up observations to further characterize the planetary system.
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| 24. |
- Van Eylen, Vincent, et al.
(författare)
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HD 89345: A bright oscillating star hosting a transiting warm Saturn-sized planet observed by K2
- 2018
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 478:4, s. 4866-4880
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery and characterization of HD 89345b (K2-234b; EPIC 248777106b), a Saturn-sized planet orbiting a slightly evolved star. HD 89345 is a bright star (V = 9.3 mag) observed by the K2 mission with 1 min time sampling. It exhibits solar-like oscillations. We conducted asteroseismology to determine the parameters of the star, finding themass and radius to be 1.12-0.01+0.04M⊙and 1.657-0.004+0.020R⊙, respectively. The star appears to have recently left the main sequence, based on the inferred age, 9.4-1.3+0.4Gyr, and the non-detection of mixed modes. The star hosts a 'warm Saturn' (P = 11.8 d, Rp= 6.86 ± 0.14 R⊕). Radial-velocity follow-up observations performed with the FIbre-fed Echelle Spectrograph, HARPS, and HARPS-N spectrographs show that the planet has a mass of 35.7 ± 3.3 M⊕. The data also show that the planet's orbit is eccentric (e≈0.2). An investigation of the rotational splitting of the oscillation frequencies of the star yields no conclusive evidence on the stellar inclination angle. We further obtained Rossiter-McLaughlin observations, which result in a broad posterior of the stellar obliquity. The planet seems to confirm to the same patterns that have been observed for other sub-Saturns regarding planet mass and multiplicity, orbital eccentricity, and stellar metallicity.
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| 25. |
- Mahajan, Anubha, et al.
(författare)
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Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus.
- 2015
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.
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| 26. |
- Niraula, P., et al.
(författare)
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Three Super-Earths Transiting the Nearby Star GJ 9827
- 2017
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 154:6, s. 266-
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Tidskriftsartikel (refereegranskat)abstract
- We report on the discovery of three transiting planets around GJ 9827. The planets have radii of 1.75 ± 0.18, 1.36 ± 0.14, and 2.11_-0.21^+0.22 R⊕, and periods of 1.20896, 3.6480, and 6.2014 days, respectively. The detection was made in Campaign 12 observations as part of our K2 survey of nearby stars. GJ 9827 is a V = 10.39 mag K6V star at a distance of 30.3 ± 1.6 parsecs and the nearest star to be found hosting planets by Kepler and K2. The radial velocity follow-up, high-resolution imaging, and detection of multiple transiting objects near commensurability drastically reduce the false positive probability. The orbital periods of GJ 9827 b, c, and d planets are very close to the 1:3:5 mean motion resonance. Our preliminary analysis shows that GJ 9827 planets are excellent candidates for atmospheric observations. Besides, the planetary radii span both sides of the rocky and gaseous divide, hence the system will be an asset in expanding our understanding of the threshold.
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| 27. |
- Aguirre Børsen-Koch, V., et al.
(författare)
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The BAyesian STellar algorithm (BASTA) : A fitting tool for stellar studies, asteroseismology, exoplanets, and Galactic archaeology
- 2022
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 509:3, s. 4344-4364
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the public version of the BAyesian STellar Algorithm (BASTA), an open-source code written in Python to determine stellar properties based on a set of astrophysical observables. BASTA has been specifically designed to robustly combine large data sets that include asteroseismology, spectroscopy, photometry, and astrometry. We describe the large number of asteroseismic observations that can be fit by the code and how these can be combined with atmospheric properties (as well as parallaxes and apparent magnitudes), making it the most complete analysis pipeline available for oscillating main-sequence, subgiant, and red giant stars. BASTA relies on a set of pre-built stellar isochrones or a custom-designed library of stellar tracks, which can be further refined using our interpolation method (both along and across stellar tracks or isochrones). We perform recovery tests with simulated data that reveal levels of accuracy at the few percent level for radii, masses, and ages when individual oscillation frequencies are considered, and show that asteroseismic ages with statistical uncertainties below 10 per cent are within reach if our stellar models are reliable representations of stars. BASTAis extensively documented and includes a suite of examples to support easy adoption and further development by new users.
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| 28. |
- Barragán, O., et al.
(författare)
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K2-141 b: A 5-M⊕ super-Earth transiting a K7 V star every 6.7 hours
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
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Tidskriftsartikel (refereegranskat)abstract
- We report on the discovery of K2-141 b (EPIC 246393474 b), an ultra-short-period super-Earth on a 6.7 h orbit transiting an active K7 V star based on data from K2 campaign 12. We confirmed the planet's existence and measured its mass with a series of follow-up observations: seeing-limited Muscat imaging, NESSI high-resolution speckle observations, and FIES and HARPS high-precision radial-velocity monitoring. K2-141 b has a mass of 5.31 ± 0.46 M ⊗ and radius of 1.54 -0.09 +0.10 R ⊗ , yielding a mean density of 8.00 -1.45 +1.83 g cm -3 and suggesting a rocky-iron composition. Models indicate that iron cannot exceed ∼70% of the total mass. With an orbital period of only 6.7 h, K2-141 b is the shortest-period planet known to date with a precisely determined mass.
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| 29. |
- Gandolfi, D., et al.
(författare)
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TESS's first planet: A super-Earth transiting the naked-eye star π Mensae
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 619
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Tidskriftsartikel (refereegranskat)abstract
- We report on the confirmation and mass determination of π Men c, the first transiting planet discovered by NASA's TESS space mission. π Men is a naked-eye (V = 5.65 mag), quiet G0 V star that was previously known to host a sub-stellar companion (π Men b) on a longperiod (Porb = 2091 days), eccentric (e = 0.64) orbit. Using TESS time-series photometry, combined with Gaia data, published UCLES at AAT Doppler measurements, and archival HARPS at ESO-3.6m radial velocities, we found that π Men c is a close-in planet with an orbital period of Porb = 6.27 days, a mass of Mc = 4.52 ± 0.81 Mo, and a radius of Rc = 2.06 ± 0.03 Ro. Based on the planet's orbital period and size, π Men c is a super-Earth located at, or close to, the radius gap, while its mass and bulk density suggest it may have held on to a significant atmosphere. Because of the brightness of the host star, this system is highly suitable for a wide range of further studies to characterize the planetary atmosphere and dynamical properties. We also performed an asteroseismic analysis of the TESS data and detected a hint of power excess consistent with the seismic values expected for this star, although this result depends on the photometric aperture used to extract the light curve. This marginal detection is expected from pre-launch simulations hinting at the asteroseismic potential of the TESS mission for longer, multi-sector observations and/or for more evolved bright stars.
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| 30. |
- Andrikopoulos, Petros, et al.
(författare)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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| 31. |
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| 32. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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| 33. |
- Buhl, Michael E.J., et al.
(författare)
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Antimicrobial resistance surveillance of Bacteroides fragilis isolated from blood cultures, Europe, 2022 (ReSuBacfrag)
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Ingår i: International Journal of Antimicrobial Agents. - 1872-7913.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBacteroides fragilis is the most frequent cause of anaerobic bacteraemia. Although recent data suggest a rise in antimicrobial resistance (AMR) of this and other anaerobic bacteria, surveillance remains limited due to a lack of both data availability and comparability. However, a newly introduced standardised method for antimicrobial susceptibility testing (AST) of anaerobic bacteria has made larger scale surveillance possible for the first time.AimTo investigate phenotypic AMR of Bacteroides fragilis isolates from bacteraemia across Europe in 2022.MethodsIn a multicentre approach, clinical microbiology laboratories in Europe were invited to contribute results of AST for Bacteroides fragilis blood culture isolates (including only the first isolate per patient and year). AST of a selection of four antibiotics was performed locally by participating laboratories in a prospective or retrospective manner, using the new EUCAST disc diffusion method on fastidious anaerobe agar (FAA-HB).ResultsA total of 16 European countries reported antimicrobial susceptibilities in 449 unique isolates of Bacteroides fragilis from blood cultures in 2022. Clindamycin demonstrated the highest resistance rates (20.9%, range 0 - 63.6%), followed by piperacillin-tazobactam (11.1%, 0 - 54.5%), meropenem (13.4%, 0 - 45.5%), and metronidazole (1.8%, 0 - 20.0%), all with wide variation between countries.ConclusionConsidering that the mean resistance rates across Europe were higher than expected for three of the four anti-anaerobic antibiotics under surveillance, both local AST of clinically relevant isolates of Bacteroides fragilis and continued surveillance on an international level is warranted.
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| 34. |
- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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