Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Galaxy And Mass Assembly (GAMA) : structural investigation of galaxies via model analysis

We present single-Sérsic two-dimensional (2D) model fits to 167 600 galaxies modelled independently in the ugrizYJHK bandpasses using reprocessed Sloan Digital Sky Survey Data Release Seven (SDSS DR7) and UKIRT Infrared Deep Sky Survey Large Area Survey imaging data available from the Galaxy And Mass Assembly (GAMA) data base. In order to facilitate this study we developed Structural Investigation of Galaxies via Model Analysis (SIGMA), an R wrapper around several contemporary astronomy software packages including SOURCE EXTRACTOR, PSF EXTRACTOR and GALFIT 3. SIGMA produces realistic 2D model fits to galaxies, employing automatic adaptive background subtraction and empirical point spread function measurements on the fly for each galaxy in GAMA. Using these results, we define a common coverage area across the three GAMA regions containing 138 269 galaxies. We provide Sérsic magnitudes truncated at 10re which show good agreement with SDSS Petrosian and GAMA photometry for low Sérsic index systems (n 4), recovering as much as Δm= 0.5 mag in the r band. We employ a K-band Sérsic index/u−r colour relation to delineate the massive (n > ∼2) early-type galaxies (ETGs) from the late-type galaxies (LTGs). The mean Sérsic index of these ETGs shows a smooth variation with wavelength, increasing by 30 per cent from g through K. LTGs exhibit a more extreme change in Sérsic index, increasing by 52 per cent across the same range. In addition, ETGs and LTGs exhibit a 38 and 25 per cent decrease, respectively, in half-light radius from g through K. These trends are shown to arise due to the effects of dust attenuation and stellar population/metallicity gradients within galaxy populations

Galaxy And Mass Assembly (GAMA): the galaxy stellar mass function at z < 0.06

We determine the low-redshift field galaxy stellar mass function (GSMF) using an area of 143 deg2 from the first three years of the Galaxy And Mass Assembly (GAMA) survey. The magnitude limits of this redshift survey are r < 19.4 mag over two-thirds and 19.8 mag over one-third of the area. The GSMF is determined from a sample of 5210 galaxies using a density-corrected maximum volume method. This efficiently overcomes the issue of fluctuations in the number density versus redshift. With H0= 70 km s−1 Mpc−1, the GSMF is well described between 108 and 1011.5 M⊙ using a double Schechter function with Graphic, Graphic, α1=−0.35, Graphic and α2=−1.47. This result is more robust to uncertainties in the flow-model corrected redshifts than from the shallower Sloan Digital Sky Survey main sample (r < 17.8 mag). The upturn in the GSMF is also seen directly in the i-band and K-band galaxy luminosity functions. Accurately measuring the GSMF below 108 M⊙ is possible within the GAMA survey volume but as expected requires deeper imaging data to address the contribution from low surface-brightness galaxies

Galaxy And Mass Assembly (GAMA): ugrizYJHK Sérsic luminosity functions and the cosmic spectral energy distribution by Hubble type

We report the morphological classification of 3727 galaxies from the Galaxy and Mass Assembly survey with Mr < −17.4 mag and in the redshift range 0.025 < z < 0.06 (2.1 × 105 Mpc3) into E, S0-Sa, SB0-SBa, Sab-Scd, SBab-SBcd, Sd-Irr and little blue spheroid classes. Approximately 70 per cent of galaxies in our sample are disc-dominated systems, with the remaining ∼30 per cent spheroid dominated. We establish the robustness of our classifications, and use them to derive morphological-type luminosity functions and luminosity densities in the ugrizYJHK passbands, improving on prior studies that split by global colour or light profile shape alone. We find that the total galaxy luminosity function is best described by a double-Schechter function while the constituent morphological-type luminosity functions are well described by a single-Schechter function. These data are also used to derive the star formation rate densities for each Hubble class, and the attenuated and unattenuated (corrected for dust) cosmic spectral energy distributions, i.e. the instantaneous energy production budget. While the observed optical/near-IR energy budget is dominated 58:42 by galaxies with a significant spheroidal component, the actual energy production rate is reversed, i.e. the combined disc-dominated populations generate ∼1.3 times as much energy as the spheroid-dominated populations. On the grandest scale, this implies that chemical evolution in the local Universe is currently largely confined to mid-type spiral classes like our Milky Way

Galaxy and Mass Assembly (GAMA): Optimal Tiling of Dense Surveys with a Multi-Object Spectrograph

A heuristic greedy algorithm is developed for efficiently tiling spatially dense redshift surveys. In its first application to the Galaxy and Mass Assembly (GAMA) redshift survey we find it rapidly improves the spatial uniformity of our data, and naturally corrects for any spatial bias introduced by the 2dF multi-object spectrograph. We make conservative predictions for the final state of the GAMA redshift survey after our final allocation of time, and can be confident that even if worse than typical weather affects our observations, all of our main survey requirements will be met

Galaxy And Mass Assembly (GAMA): the input catalogue and star-galaxy separation

We describe the spectroscopic target selection for the Galaxy And Mass Assembly (GAMA) survey. The input catalogue is drawn from the Sloan Digital Sky Survey (SDSS) and UKIRT Infrared Deep Sky Survey (UKIDSS). The aim is to measure redshifts for galaxies in three 4x12 degree regions at 9h, 12h and 14.5h, on the celestial equator, with magnitude selections r < 19.4, z < 18.2 and K(AB) < 17.6 over all three regions, and r < 19.8 in the 12-h region. The target density is 1080 per sq. deg. in the 12-h region and 720 per sq. deg. in the other regions. The average GAMA target density and area are compared with completed and ongoing galaxy redshift surveys. The GAMA survey implements a highly complete star-galaxy separation that jointly uses an intensity-profile separator (delta(sg) = r-band psf mag - model mag) as per the SDSS) and a colour separator. The colour separator is defined as delta(sg,jk) = J - K - f(g-i), where f(g-i) is a quadratic fit to the J-K colour of the stellar locus over the range 0.3 < g-i < 2.3. All galaxy populations investigated are well separated with delta(sg,jk) > 0.2. From two years out of a three-year AAOmega program on the Anglo-Australian Telescope, we have obtained 79599 unique galaxy redshifts. Previously known redshifts in the GAMA region bring the total up to 98497. The median galaxy redshift is 0.2 with 99% at z < 0.5. We present some of the global statistical properties of the survey, including K-band galaxy counts, colour-redshift relations and preliminary n(z).Comment: 15 pages, 15 figures, accepted by MNRAS; v2 includes new figure with K-band galaxy counts, more description of UKIDSS reduction, and other minor change

Galaxy And Mass Assembly (GAMA) : galaxy environments and star formation rate variations

We present a detailed investigation into the effects of galaxy environment on their star formation rates (SFRs) using galaxies observed in the Galaxy And Mass Assembly (GAMA) survey. We use three independent volume-limited samples of galaxies within z < 0.2 and Mr < −17.8. We investigate the known SFR–density relationship and explore in detail the dependence of SFR on stellar mass and density. We show that the SFR–density trend is only visible when we include the passive galaxy population along with the star-forming population. This SFR–density relation is absent when we consider only the star-forming population of galaxies, consistent with previous work. While there is a strong dependence of the EWHα on density we find, as in previous studies, that these trends are largely due to the passive galaxy population and this relationship is absent when considering a ‘star-forming’ sample of galaxies. We find that stellar mass has the strongest influence on SFR and EWHα with the environment having no significant effect on the star formation properties of the star-forming population. We also show that the SFR–density relationship is absent for both early- and late-type star-forming galaxies. We conclude that the stellar mass has the largest impact on the current SFR of a galaxy, and any environmental effect is not detectable. The observation that the trends with density are due to the changing morphology fraction with density implies that the time-scales must be very short for any quenching of the SFR in infalling galaxies. Alternatively, galaxies may in fact undergo predominantly in situ evolution where the infall and quenching of galaxies from the field into dense environments is not the dominant evolutionary mode

Galaxy and Mass Assembly (GAMA): the GAMA galaxy group catalogue (G3^3Cv1)

Using the complete GAMA-I survey covering ~142 sq. deg. to r=19.4, of which ~47 sq. deg. is to r=19.8, we create the GAMA-I galaxy group catalogue (G3Cv1), generated using a friends-of-friends (FoF) based grouping algorithm. Our algorithm has been tested extensively on one family of mock GAMA lightcones, constructed from Lambda-CDM N-body simulations populated with semi-analytic galaxies. Recovered group properties are robust to the effects of interlopers and are median unbiased in the most important respects. G3Cv1 contains 14,388 galaxy groups (with multiplicity >= 2$), including 44,186 galaxies out of a possible 110,192 galaxies, implying ~40% of all galaxies are assigned to a group. The similarities of the mock group catalogues and G3Cv1 are multiple: global characteristics are in general well recovered. However, we do find a noticeable deficit in the number of high multiplicity groups in GAMA compared to the mocks. Additionally, despite exceptionally good local spatial completeness, G3Cv1 contains significantly fewer compact groups with 5 or more members, this effect becoming most evident for high multiplicity systems. These two differences are most likely due to limitations in the physics included of the current GAMA lightcone mock. Further studies using a variety of galaxy formation models are required to confirm their exact origin.Comment: 31 pages, 22 figures (lo-res astro-ph, hi-res on demand or via MNRAS), accepted for publication in MNRA

Galaxy and mass assembly (GAMA): colour- and luminosity-dependent clustering from calibrated photometric redshifts

We measure the two-point angular correlation function of a sample of 4289 223 galaxies with r < 19.4 mag from the Sloan Digital Sky Survey (SDSS) as a function of photometric redshift, absolute magnitude and colour down to Mr − 5 log h = −14 mag. Photometric redshifts are estimated from ugriz model magnitudes and two Petrosian radii using the artificial neural network package ANNz, taking advantage of the Galaxy And Mass Assembly (GAMA) spectroscopic sample as our training set. These photometric redshifts are then used to determine absolute magnitudes and colours. For all our samples, we estimate the underlying redshift and absolute magnitude distributions using Monte Carlo resampling. These redshift distributions are used in Limber's equation to obtain spatial correlation function parameters from power-law fits to the angular correlation function. We confirm an increase in clustering strength for sub-L* red galaxies compared with ∼L* red galaxies at small scales in all redshift bins, whereas for the blue population the correlation length is almost independent of luminosity for ∼L* galaxies and fainter. A linear relation between relative bias and log luminosity is found to hold down to luminosities L ∼ 0.03L*. We find that the redshift dependence of the bias of the L* population can be described by the passive evolution model of Tegmark & Peebles. A visual inspection of a random sample from our r < 19.4 sample of SDSS galaxies reveals that about 10 per cent are spurious, with a higher contamination rate towards very faint absolute magnitudes due to over-deblended nearby galaxies. We correct for this contamination in our clustering analysis

Galaxy and Mass Assembly (GAMA): galaxies at the faint end of the Hα\alpha luminosity function

We present an analysis of the properties of the lowest Halpha-luminosity galaxies (L_Halpha<4x10^32 W; SFR<0.02 Msun/yr) in the Galaxy And Mass Assembly (GAMA) survey. These galaxies make up the the rise above a Schechter function in the number density of systems seen at the faint end of the Halpha luminosity function. Above our flux limit we find that these galaxies are principally composed of intrinsically low stellar mass systems (median stellar mass =2.5x10^8 Msun) with only 5/90 having stellar masses M>10^10 Msun. The low SFR systems are found to exist predominantly in the lowest density environments (median density ~0.02 galaxy Mpc^-2 with none in environments more dense than ~1.5 galaxy Mpc^-2). Their current specific star formation rates (SSFR; -8.5 < log(SSFR[yr^-1])<-12.) are consistent with their having had a variety of star formation histories. The low density environments of these galaxies demonstrates that such low-mass, star-forming systems can only remain as low-mass and forming stars if they reside sufficiently far from other galaxies to avoid being accreted, dispersed through tidal effects or having their gas reservoirs rendered ineffective through external processes