J-PLUS: The javalambre photometric local universe survey

ABSTRACT: TheJavalambrePhotometric Local UniverseSurvey (J-PLUS )isanongoing 12-band photometricopticalsurvey, observingthousands of squaredegrees of theNorthernHemispherefromthededicated JAST/T80 telescope at the Observatorio Astrofísico de Javalambre (OAJ). The T80Cam is a camera with a field of view of 2 deg2 mountedon a telescopewith a diameter of 83 cm, and isequippedwith a uniquesystem of filtersspanningtheentireopticalrange (3500–10 000 Å). Thisfiltersystemis a combination of broad-, medium-, and narrow-band filters, optimallydesigned to extracttherest-framespectralfeatures (the 3700–4000 Å Balmer break region, Hδ, Ca H+K, the G band, and the Mg b and Ca triplets) that are key to characterizingstellartypes and delivering a low-resolutionphotospectrumforeach pixel of theobservedsky. With a typicaldepth of AB ∼21.25 mag per band, thisfilter set thusallowsforanunbiased and accuratecharacterization of thestellarpopulation in our Galaxy, itprovidesanunprecedented 2D photospectralinformationforall resolved galaxies in the local Universe, as well as accuratephoto-z estimates (at the δ z/(1 + z)∼0.005–0.03 precisionlevel) formoderatelybright (up to r ∼ 20 mag) extragalacticsources. Whilesomenarrow-band filters are designedforthestudy of particular emissionfeatures ([O II]/λ3727, Hα/λ6563) up to z < 0.017, theyalsoprovidewell-definedwindowsfortheanalysis of otheremissionlines at higherredshifts. As a result, J-PLUS has thepotential to contribute to a widerange of fields in Astrophysics, both in thenearbyUniverse (MilkyWaystructure, globular clusters, 2D IFU-likestudies, stellarpopulations of nearby and moderate-redshiftgalaxies, clusters of galaxies) and at highredshifts (emission-line galaxies at z ≈ 0.77, 2.2, and 4.4, quasi-stellarobjects, etc.). Withthispaper, wereleasethefirst∼1000 deg2 of J-PLUS data, containingabout 4.3 millionstars and 3.0 milliongalaxies at r <  21mag. With a goal of 8500 deg2 forthe total J-PLUS footprint, thesenumbers are expected to rise to about 35 millionstars and 24 milliongalaxiesbytheend of thesurvey.Funding for the J-PLUS Project has been provided by the Governments of Spain and Aragón through the Fondo de Inversiones de Teruel, the Spanish Ministry of Economy and Competitiveness (MINECO; under grants AYA2017-86274-P, AYA2016-77846-P, AYA2016-77237-C3-1-P, AYA2015-66211-C2-1-P, AYA2015-66211-C2-2, AYA2012-30789, AGAUR grant SGR-661/2017, and ICTS-2009-14), and European FEDER funding (FCDD10-4E-867, FCDD13-4E-2685

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

J-PLUS: The Javalambre Photometric Local Universe Survey

The Javalambre Photometric Local Universe Survey (J-PLUS) is an ongoing 12-band photometric optical survey, observing thousands of square degrees of the Northern Hemisphere from the dedicated JAST/T80 telescope at the Observatorio Astrofisico de Javalambre (OAJ). The T80Cam is a camera with a field of view of 2 deg(2) mounted on a telescope with a diameter of 83 cm, and is equipped with a unique system of filters spanning the entire optical range (3500-10 000 angstrom). This filter system is a combination of broad-, medium-, and narrow-band filters, optimally designed to extract the rest-frame spectral features (the 3700-4000 angstrom Balmer break region, H delta, Ca H+K, the G band, and the Mg b and Ca triplets) that are key to characterizing stellar types and delivering a low-resolution photospectrum for each pixel of the observed sky. With a typical depth of AB similar to 21.25 mag per band, this filter set thus allows for an unbiased and accurate characterization of the stellar population in our Galaxy, it provides an unprecedented 2D photospectral information for all resolved galaxies in the local Universe, as well as accurate photo-z estimates (at the delta z/(1 + z) similar to 0.005-0.03 precision level) for moderately bright (up to r similar to 20 mag) extragalactic sources. While some narrow-band filters are designed for the study of particular emission features ([O II]/lambda 3727, H alpha/lambda 6563) up to z < 0.017, they also provide well-defined windows for the analysis of other emission lines at higher redshifts. As a result, J-PLUS has the potential to contribute to a wide range of fields in Astrophysics, both in the nearby Universe (Milky Way structure, globular clusters, 2D IFU-like studies, stellar populations of nearby and moderate-redshift galaxies, clusters of galaxies) and at high redshifts (emission-line galaxies at z approximate to 0.77, 2.2, and 4.4, quasi-stellar objects, etc.). With this paper, we release the first similar to 1000 deg(2) of J-PLUS data, containing about 4.3 million stars and 3.0 million galaxies at r < 21 mag. With a goal of 8500 deg(2) for the total J-PLUS footprint, these numbers are expected to rise to about 35 million stars and 24 million galaxies by the end of the survey

Consensus document on dog and cat allergy.

The prevalence of sensitization to dogs and cats varies by country, exposure time and predisposition to atopy. It is estimated that 26% of European adults coming to the clinic for suspected allergy to inhalant allergens are sensitized to cats and 27% to dogs. This document is intended to be a useful tool for clinicians involved in the management of people with dog or cat allergy. It was prepared from a consensus process based on the RAND/UCLA method. Following a literature review, it proposes various recommendations concerning the diagnosis and treatment of these patients, grounded in evidence and clinical experience. The diagnosis of dog and cat allergy is based on a medical history and physical examination that are consistent with each other and is confirmed with positive results on specific IgE skin tests. Sometimes, especially in polysensitized patients, molecular diagnosis is strongly recommended. Although the most advisable measure would be to avoid the animal, this is often impossible and associated with a major emotional impact. Furthermore, indirect exposure to allergens occurs in environments in which animals are not present. Immunotherapy is emerging as a potential solution to this problem, although further supporting studies are needed

Novel genes and sex differences in COVID-19 severity.

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p &lt; 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p =&nbsp;1.3x10-22 and p =&nbsp;8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p =&nbsp;4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p =&nbsp;2.7x10-8) and ARHGAP33 (p =&nbsp;1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (&lt;60 or ≥ 60&nbsp;years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided

Novel genes and sex differences in COVID-19 severity.

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)