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Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
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.
Geschichts- und Literaturwissenschaft, verstanden als Spezialdiskurse, stehen, so die an dieser Stelle vertretene These, in einem wechselseitig-kommunikativen Verhältnis, das sich sowohl im außerwissenschaftlichen Interdiskurs Literatur als auch im Interdiskurs Geschichtserzählung niederschlägt. Die interdiskursive Konstruiertheit beider Erzähltextformen zeigt sich nicht nur inhaltlich an referentiellen Bezügen, sondern oftmals auch an (gemeinsamen) Erzählformen oder an paratextuellen Elementen. In den nachfolgenden Überlegungen werden die Interferenzen von Geschichtserzählungen und historischen Romanen in den Blick genommen, um an geeigneten Beispielen die konkrete Überführung von Spezialwissen in einen Interdiskurs aufzuzeigen und zu diskutieren. Zugleich soll ein Vergleichsrahmen eröffnet werden, der die Interdiskursivität beziehungsweise interdiskursive Konstruiertheit von Historiografie und Literatur einander gegenübergestellt. Dabei müssen diskursanalytische und narratologische Ansätze miteinander verbunden werden, um der Komplexität des Untersuchungsgegenstandes gerecht werden zu können. Die zu berücksichtigende Textauswahl beschränkt sich auf die zwei Romane "Imperium" und "Der Komet" und den geschichtswissenschaftlichen Text "The Boy", die in unterschiedlicher Weise interdiskursiv konstruiert sind. Beide Romane, und das ist neben einem allgemein historischen Sujet eines der wenigen inhaltlich verbindenden Elemente, verweisen in der fiktionalen Erzählung an verschiedenen Stellen auf Adolf Hitler und den Nationalsozialismus, und auch die faktuale Erzählung "The Boy" – erkennbar bereits am Untertitel "A Holocaust Story" – setzt sich mit dem Nationalsozialismus auseinander.