Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Overview of the DESI Legacy Imaging Surveys

The DESI Legacy Imaging Surveys (http://legacysurvey.org/) are a combination of three public projects (the Dark Energy Camera Legacy Survey, the Beijing–Arizona Sky Survey, and the Mayall z-band Legacy Survey) that will jointly image ≈14,000 deg2 of the extragalactic sky visible from the northern hemisphere in three optical bands (g, r, and z) using telescopes at the Kitt Peak National Observatory and the Cerro Tololo Inter-American Observatory. The combined survey footprint is split into two contiguous areas by the Galactic plane. The optical imaging is conducted using a unique strategy of dynamically adjusting the exposure times and pointing selection during observing that results in a survey of nearly uniform depth. In addition to calibrated images, the project is delivering a catalog, constructed by using a probabilistic inference-based approach to estimate source shapes and brightnesses. The catalog includes photometry from the grz optical bands and from four mid-infrared bands (at 3.4, 4.6, 12, and 22 μm) observed by the Wide-field Infrared Survey Explorer satellite during its full operational lifetime. The project plans two public data releases each year. All the software used to generate the catalogs is also released with the data. This paper provides an overview of the Legacy Surveys project

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Calibrations of the Compton Spectrometer and Imager

The Compton Spectrometer and Imager (COSI) is a balloon-borne soft $\gamma$-ray telescope (0.2-5 MeV) designed to study astrophysical sources. COSI employs a compact Compton telescope design and is comprised of twelve high-purity germanium semiconductor detectors. Tracking the locations and energies of $\gamma$-ray scatters within the detectors permits high-resolution spectroscopy, direct imaging over a wide field-of-view, polarization studies, and effective suppression of background events. Critical to the precise determination of each interaction's energy, position, and the subsequent event reconstruction are several calibrations conducted in the field before launch. Additionally, benchmarking the instrument's higher-level performance through studies of its angular resolution, effective area, and polarization sensitivity quantifies COSI's scientific capabilities. In May 2016, COSI became the first science payload to be launched on NASA's superpressure balloon and was slated for launch again in April 2020. Though the 2020 launch was canceled due to the COVID-19 pandemic, the COSI team took calibration measurements prior to cancellation. In this paper we provide a detailed overview of COSI instrumentation, describe the calibration methods, and compare the calibration and benchmarking results of the 2016 and 2020 balloon campaigns. These procedures will be integral to the calibration and benchmarking of the NASA Small Explorer satellite version of COSI scheduled to launch in 2025.Comment: 29 pages, 22 figures, accepted by Nuclear Instruments and Methods in Physics Research Section