| 1. |
- Ahluwalia, T. S., et al.
(författare)
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Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- 2021
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:5, s. 393-409
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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| 2. |
- Brennan, S. J., et al.
(författare)
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Photometric and spectroscopic evolution of the interacting transient AT 2016jbu(Gaia16cfr)
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 5642-5665
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Tidskriftsartikel (refereegranskat)abstract
- We present the results from a high-cadence, multiwavelength observation campaign of AT 2016jbu (aka Gaia16cfr), an interacting transient. This data set complements the current literature by adding higher cadence as well as extended coverage of the light-curve evolution and late-time spectroscopic evolution. Photometric coverage reveals that AT 2016jbu underwent significant photometric variability followed by two luminous events, the latter of which reached an absolute magnitude of MV ∼ −18.5 mag. This is similar to the transient SN 2009ip whose nature is still debated. Spectra are dominated by narrow emission lines and show a blue continuum during the peak of the second event. AT 2016jbu shows signatures of a complex, non-homogeneous circumstellar material (CSM). We see slowly evolving asymmetric hydrogen line profiles, with velocities of 500 km s−1 seen in narrow emission features from a slow-moving CSM, and up to 10 000 km s−1 seen in broad absorption from some high-velocity material. Late-time spectra (∼+1 yr) show a lack of forbidden emission lines expected from a core-collapse supernova and are dominated by strong emission from H, He I, and Ca II. Strong asymmetric emission features, a bumpy light curve, and continually evolving spectra suggest an inhibit nebular phase. We compare the evolution of H α among SN 2009ip-like transients and find possible evidence for orientation angle effects. The light-curve evolution of AT 2016jbu suggests similar, but not identical, circumstellar environments to other SN 2009ip-like transients.
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| 3. |
- Brennan, S. J., et al.
(författare)
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Progenitor, environment, and modelling of the interacting transient AT 2016jbu (Gaia16cfr)
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 5666-5685
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Tidskriftsartikel (refereegranskat)abstract
- We present the bolometric light curve, identification and analysis of the progenitor candidate, and preliminary modelling of AT 2016jbu (Gaia16cfr). We find a progenitor consistent with a ∼ 22–25 M⊙ yellow hypergiant surrounded by a dusty circumstellar shell, in agreement with what has been previously reported. We see evidence for significant photometric variability in the progenitor, as well as strong Hα emission consistent with pre-existing circumstellar material. The age of the environment, as well as the resolved stellar population surrounding AT 2016jbu, supports a progenitor age of >10 Myr, consistent with a progenitor mass of ∼22 M⊙. A joint analysis of the velocity evolution of AT 2016jbu and the photospheric radius inferred from the bolometric light curve shows the transient is consistent with two successive outbursts/explosions. The first outburst ejected material with velocity ∼650 km s−1, while the second, more energetic event ejected material at ∼4500 km s−1. Whether the latter is the core collapse of the progenitor remains uncertain. We place a limit on the ejected 56Ni mass of <0.016 M⊙. Using the Binary Population And Spectral Synthesis (BPASS) code, we explore a wide range of possible progenitor systems and find that the majority of these are in binaries, some of which are undergoing mass transfer or common-envelope evolution immediately prior to explosion. Finally, we use the SuperNova Explosion Code (SNEC) to demonstrate that the low-energy explosions within some of these binary systems, together with sufficient circumstellar material, can reproduce the overall morphology of the light curve of AT 2016jbu.
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| 4. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 5. |
- Abazajian, Kevork, et al.
(författare)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 6. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 7. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 8. |
- Hori, Yasunori, et al.
(författare)
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The Discovery and Follow-up of Four Transiting Short-period Sub-Neptunes Orbiting M Dwarfs
- 2024
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Ingår i: Astronomical Journal. - 1538-3881 .- 0004-6256. ; 167:6
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Tidskriftsartikel (refereegranskat)abstract
- Sub-Neptunes with radii of 2-3 R ⊕ are intermediate in size between rocky planets and Neptune-sized planets. The orbital properties and bulk compositions of transiting sub-Neptunes provide clues to the formation and evolution of close-in small planets. In this paper, we present the discovery and follow-up of four sub-Neptunes orbiting M dwarfs (TOI-782, TOI-1448, TOI-2120, and TOI-2406), three of which were newly validated by ground-based follow-up observations and statistical analyses. TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b have radii of R p = 2.740 − 0.079 + 0.082 R ⊕ , 2.769 − 0.068 + 0.073 R ⊕ , 2.120 ± 0.067 R ⊕, and 2.830 − 0.066 + 0.068 R ⊕ and orbital periods of P = 8.02, 8.11, 5.80, and 3.08 days, respectively. Doppler monitoring with the Subaru/InfraRed Doppler instrument led to 2σ upper limits on the masses of <19.1 M ⊕, <19.5 M ⊕, <6.8 M ⊕, and <15.6 M ⊕ for TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b, respectively. The mass-radius relationship of these four sub-Neptunes testifies to the existence of volatile material in their interiors. These four sub-Neptunes, which are located above the so-called “radius valley,” are likely to retain a significant atmosphere and/or an icy mantle on the core, such as a water world. We find that at least three of the four sub-Neptunes (TOI-782 b, TOI-2120 b, and TOI-2406 b), orbiting M dwarfs older than 1 Gyr, are likely to have eccentricities of e ∼ 0.2-0.3. The fact that tidal circularization of their orbits is not achieved over 1 Gyr suggests inefficient tidal dissipation in their interiors.
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| 9. |
- Jencson, Jacob E., et al.
(författare)
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AT 2019qyl in NGC 300 : Internal Collisions in the Early Outflow from a Very Fast Nova in a Symbiotic Binary
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 920:2
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Tidskriftsartikel (refereegranskat)abstract
- Nova eruptions, thermonuclear explosions on the surfaces of white dwarfs (WDs), are now recognized to be among the most common shock-powered astrophysical transients. We present the early discovery and rapid ultraviolet (UV), optical, and infrared (IR) temporal development of AT 2019qyl, a recent nova in the nearby Sculptor Group galaxy NGC 300. The light curve shows a rapid rise lasting ≲1 day, reaching a peak absolute magnitude of MV = −9.2 mag and a very fast decline, fading by 2 mag over 3.5 days. A steep dropoff in the light curves after 71 days and the rapid decline timescale suggest a low-mass ejection from a massive WD with MWD ≳ 1.2 M⊙. We present an unprecedented view of the early spectroscopic evolution of such an event. Three spectra prior to the peak reveal a complex, multicomponent outflow giving rise to internal collisions and shocks in the ejecta of an He/N-class nova. We identify a coincident IR-variable counterpart in the extensive preeruption coverage of the transient location and infer the presence of a symbiotic progenitor system with an O-rich asymptotic-giant-branch donor star, as well as evidence for an earlier UV-bright outburst in 2014. We suggest that AT 2019qyl is analogous to the subset of Galactic recurrent novae with red-giant companions such as RS Oph and other embedded nova systems like V407 Cyg. Our observations provide new evidence that internal shocks between multiple, distinct outflow components likely contribute to the generation of the shock-powered emission from such systems.
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| 10. |
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