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The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
In the past two decades, pions created in the high density regions of heavy ion collisions have been predicted to be sensitive at high densities to the symmetry energy term in the nuclear equation of state, a property that is key to our understanding of neutron stars. In a new experiment designed to study the symmetry energy, the multiplicities of negatively and positively charged pions have been measured with high accuracy for central 132Sn+124Sn, 112Sn+124Sn, and 108Sn+112Sn collisions at E/A = 270 MeV with the SπRIT Time Projection Chamber. While individual pion multiplicities are measured to 4% accuracy, those of the charged pion multiplicity ratios are measured to 2% accuracy. We compare these data to predictions from seven major transport models. The calculations reproduce qualitatively the dependence of the multiplicities and their ratios on the total neutron and proton number in the colliding systems. However, the predictions of the transport models from different codes differ too much to allow extraction of reliable constraints on the symmetry energy from the data. This finding may explain previous contradictory conclusions on symmetry energy constraints obtained from pion data in Au+Au system. These new results call for still better understanding of the differences among transport codes, and new observables that are more sensitive to the density dependence of the symmetry energy.
Congenital diaphragmatic hernia (CDH) is a relatively common and life-threatening birth defect, characterized by incomplete formation of the diaphragm. Because CDH herniation occurs at the same time as preacinar airway branching, normal lung development becomes severely disrupted, resulting almost invariably in pulmonary hypoplasia. Despite various research efforts over the past decades, the pathogenesis of CDH and associated lung hypoplasia remains poorly understood. With the advent of molecular techniques, transgenic animal models of CDH have generated a large number of candidate genes, thus providing a novel basis for future research and treatment. This review article offers a comprehensive overview of genes and signaling pathways implicated in CDH etiology, whilst also discussing strengths and limitations of transgenic animal models in relation to the human condition.