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- Ramdas, S., et al.
(author)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Journal article (peer-reviewed)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 5. |
- Winkler, TW, et al.
(author)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 7. |
- Osborn, H. P., et al.
(author)
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Uncovering the true periods of the young sub-Neptunes orbiting TOI-2076
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 664
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Journal article (peer-reviewed)abstract
- Context. TOI-2076 is a transiting three-planet system of sub-Neptunes orbiting a bright (G = 8.9 mag), young (340 +/- 80 Myr) K-type star. Although a validated planetary system, the orbits of the two outer planets were unconstrained as only two non-consecutive transits were seen in TESS photometry. This left 11 and 7 possible period aliases for each. Aims. To reveal the true orbits of these two long-period planets, precise photometry targeted on the highest-probability period aliases is required. Long-term monitoring of transits in multi-planet systems can also help constrain planetary masses through TTV measurements. Methods. We used the MonoTools package to determine which aliases to follow, and then performed space-based and ground-based photometric follow-up of TOI-2076 c and d with CHEOPS, SAINT-EX, and LCO telescopes. Results. CHEOPS observations revealed a clear detection for TOI-2076 c at P = 21.01538(-0.00074)(+0.00084) d, and allowed us to rule out three of the most likely period aliases for TOI-2076 d. Ground-based photometry further enabled us to rule out remaining aliases and confirm the P = 35.12537 +/- 0.00067 d alias. These observations also improved the radius precision of all three sub-Neptunes to 2.518 +/- 0.036, 3.497 +/- 0.043, and 3.232 +/- 0.063 R-circle plus. Our observations also revealed a clear anti-correlated TTV signal between planets b and c likely caused by their proximity to the 2:1 resonance, while planets c and d appear close to a 5:3 period commensurability, although model degeneracy meant we were unable to retrieve robust TTV masses. Their inflated radii, likely due to extended H-He atmospheres, combined with low insolation makes all three planets excellent candidates for future comparative transmission spectroscopy with JWST.
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- Harre, J. V., et al.
(author)
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Examining the orbital decay targets KELT-9 b, KELT-16 b, and WASP-4 b, and the transit-timing variations of HD 97658 b
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 669
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Journal article (peer-reviewed)abstract
- Context. Tidal orbital decay is suspected to occur for hot Jupiters in particular, with the only observationally confirmed case of this being WASP-12 b. By examining this effect, information on the properties of the host star can be obtained using the so-called stellar modified tidal quality factor Q′∗, which describes the efficiency with which the kinetic energy of the planet is dissipated within the star. This can provide information about the interior of the star. Aims. In this study, we aim to improve constraints on the tidal decay of the KELT-9, KELT-16, and WASP-4 systems in order to find evidence for or against the presence of tidal orbital decay. With this, we want to constrain the Q′∗ value for each star. In addition, we aim to test the existence of the transit timing variations (TTVs) in the HD 97658 system, which previously favoured a quadratic trend with increasing orbital period. Methods. Making use of newly acquired photometric observations from CHEOPS (CHaracterising ExOplanet Satellite) and TESS (Transiting Exoplanet Survey Satellite), combined with archival transit and occultation data, we use Markov chain Monte Carlo (MCMC) algorithms to fit three models to the data, namely a constant-period model, an orbital-decay model, and an apsidal-precession model. Results. We find that the KELT-9 system is best described by an apsidal-precession model for now, with an orbital decay trend at over 2 σ being a possible solution as well. A Keplerian orbit model with a constant orbital period provides the best fit to the transit timings of KELT-16 b because of the scatter and scale of their error bars. The WASP-4 system is best represented by an orbital decay model at a 5 σ significance, although apsidal precession cannot be ruled out with the present data. For HD 97658 b, using recently acquired transit observations, we find no conclusive evidence for a previously suspected strong quadratic trend in the data.
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- Serrano, L. M., et al.
(author)
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The HD 93963 A transiting system: A 1.04d super-Earth and a 3.65 d sub-Neptune discovered by TESS and CHEOPS
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667
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Journal article (peer-reviewed)abstract
- We present the discovery of two small planets transiting HD 93963A (TOI-1797), a GOV star (M-* = 1.109 +/- 0.043M(circle dot), R-* = 1.043 +/- 0.009 R-circle dot) in a visual binary system. We combined TESS and CHEOPS space-borne photometry with MuSCAT 2 ground-based photometry, 'Alopeke and PHARO high-resolution imaging, TRES and FIES reconnaissance spectroscopy, and SOPHIE radial velocity measurements. We validated and spectroscopically confirmed the outer transiting planet HD 93963 A c, a sub-Neptune with an orbital period of P-c approximate to 3.65 d that was reported to be a TESS object of interest (TOI) shortly after the release of Sector 22 data. HD 93963 A c has amass of M-c = 19.2 +/- 4.1 M-circle plus and a radius of R-c = 3.228 +/- 0.059 R-circle plus, implying a mean density of rho(c) = 3.1 +/- 0.7 g cm(-3). The inner object, HD 93963 A b, is a validated 1.04 d ultra-short period (USP) transiting super-Earth that we discovered in the TESS light curve and that was not listed as a TOI, owing to the low significance of its signal (TESS signal-to-noise ratio approximate to 6.7, TESS + CHEOPS combined transit depth D-b = 141.5(-8.3)(+8.5) ppm). We intensively monitored the star with CHEOPS by performing nine transit observations to confirm the presence of the inner planet and validate the system. HD 93963 A b is the first small (R-b = 1.35 +/- 0.042 R-circle plus) USP planet discovered and validated by TESS and CHEOPS. Unlike planet c, HD 93963 Ab is not significantly detected in our radial velocities (M-b = 7.8 +/- 3.2 M-circle plus). The two planets are on either side of the radius valley, implying that they could have undergone completely different evolution processes. We also discovered a linear trend in our Doppler measurements, suggesting the possible presence of a long-period outer planet. With a V-band magnitude of 9.2, HD 93963 A is among the brightest stars known to host a USP planet, making it one of the most favourable targets for precise mass measurement via Doppler spectroscopy and an important laboratory to test formation, evolution, and migration models of planetary systems hosting ultra-short period planets.
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