Genetic Associations and Architecture of Asthma-COPD Overlap

BACKGROUND: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. RESEARCH QUESTION: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? STUDY DESIGN AND METHODS: We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10-6) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2). RESULTS: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10-8) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent. INTERPRETATION: We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Search for Gravitational Waves Associated with Gamma-Ray Bursts during the First Advanced LIGO Observing Run and Implications for the Origin of GRB 150906B

We present the results of the search for gravitational waves (GWs) associated with γ-ray bursts detected during the first observing run of the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO). We find no evidence of a GW signal for any of the 41 γ-ray bursts for which LIGO data are available with sufficient duration. For all γ-ray bursts, we place lower bounds on the distance to the source using the optimistic assumption that GWs with an energy of ${10}^{-2}{M}_{\odot }{c}^{2}$ were emitted within the $16$–$500$ Hz band, and we find a median 90% confidence limit of 71 Mpc at 150 Hz. For the subset of 19 short/hard γ-ray bursts, we place lower bounds on distance with a median 90% confidence limit of 90 Mpc for binary neutron star (BNS) coalescences, and 150 and 139 Mpc for neutron star–black hole coalescences with spins aligned to the orbital angular momentum and in a generic configuration, respectively. These are the highest distance limits ever achieved by GW searches. We also discuss in detail the results of the search for GWs associated with GRB 150906B, an event that was localized by the InterPlanetary Network near the local galaxy NGC 3313, which is at a luminosity distance of $54$ Mpc (z = 0.0124). Assuming the γ-ray emission is beamed with a jet half-opening angle $\leqslant 30^\circ$, we exclude a BNS and a neutron star–black hole in NGC 3313 as the progenitor of this event with confidence >99%. Further, we exclude such progenitors up to a distance of 102 Mpc and 170 Mpc, respectively

Binary Black Hole Mergers in the first Advanced LIGO Observing Run

The first observational run of the Advanced LIGO detectors, from September 12, 2015 to January 19, 2016, saw the first detections of gravitational waves from binary black hole mergers. In this paper we present full results from a search for binary black hole merger signals with total masses up to $100 M_\odot$ and detailed implications from our observations of these systems. Our search, based on general-relativistic models of gravitational wave signals from binary black hole systems, unambiguously identified two signals, GW150914 and GW151226, with a significance of greater than $5\sigma$ over the observing period. It also identified a third possible signal, LVT151012, with substantially lower significance, which has a 87% probability of being of astrophysical origin. We provide detailed estimates of the parameters of the observed systems. Both GW150914 and GW151226 provide an unprecedented opportunity to study the two-body motion of a compact-object binary in the large velocity, highly nonlinear regime. We do not observe any deviations from general relativity, and place improved empirical bounds on several high-order post-Newtonian coefficients. From our observations we infer stellar-mass binary black hole merger rates lying in the range $9-240 \mathrm{Gpc}^{-3} \mathrm{yr}^{-1}$. These observations are beginning to inform astrophysical predictions of binary black hole formation rates, and indicate that future observing runs of the Advanced detector network will yield many more gravitational wave detections

Observation of Gravitational Waves from a Binary Black Hole Merger

On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of 1.0 × 10−21. It matches the waveform predicted by general relativity for the inspiral and merger of a pair of black holes and the ringdown of the resulting single black hole. The signal was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203 000 years, equivalent to a significance greater than 5.1σ. The source lies at a luminosity distance of 410þ160 −180 Mpc corresponding to a redshift z ¼ 0.09þ0.03 −0.04 . In the source frame, the initial black hole masses are 36þ5 −4M⊙ and 29þ4 −4M⊙, and the final black hole mass is 62þ4 −4M⊙, with 3.0þ0.5 −0.5M⊙c2 radiated in gravitational waves. All uncertainties define 90% credible intervals. These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first direct detection of gravitational waves and the first observation of a binary black hole merger