Mapping the human genetic architecture of COVID-19

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-19(1,2), 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 across19 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 diseases(3-7). 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.Peer reviewe

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Implicaciones tributarias en la adopción por primera vez de NIIF y comparación de estas con las disposiciones tributarias vigentes en El Salvador.

La aplicación de las Normas Internacionales de Información Financiera para Pequeñas y Medianas Entidades, trae consigo muchas ventajas, tales como, mayor credibilidad y confiabilidad en la información financiera presentada, además de la comparabilidad de la información por ser presentada bajo estándares de normas internacionales, lo que permite su fácil comparación con otras entidades sin importar la nacionalidad de la misma; teniendo en cuenta su contexto. Sin embargo, los procedimientos o tratamientos estipulados en la normativa técnica no siempre coinciden con los establecidos en la legislación tributaria local, por lo que se hace necesario conciliar ambas partes, con el fin de mantener la integridad de la información financiera presentada sin olvidar lo establecido en la legislación tributaria local. Para el Estado, el propósito por el cual crea la legislación tributaria es para que los tributos lleguen a las arcas de este, por lo que establece cual debe ser la base sobre que se calcularan los tributos, a esta se le conoce como “base imponible”, pero la base técnica no fue creada con este mismo fin, por lo que en muchas ocasiones no coincide con la legislación tributaria local; es ahí donde el Contador Público debe estar listo para poder hacer frente a dicha situación, manteniendo la integridad de la información a través del cumplimiento de la Normativa Técnica y cumpliendo las obligaciones formales y sustantivas descritas en la legislación tributaria. Se debe tener claro que, independientemente de la base técnica utilizada para el registro y presentación de la información financiera, indefectiblemente las entidades están obligadas a cumplir con todas las disposiciones de la legislación tributaria salvadoreña, por lo que las implicaciones tributarias en la adopción de un nuevo marco de referencia para la información financiera, estarían dadas en su mayoría por el hecho de tener que llevar un serie de controles específicos, donde la información financiera presentada difiere de la base imponible para el cálculo de impuestos, dichos controles son esenciales para demostrar a la Administración Tributaria el cumplimiento de las disposiciones legales; un ejemplo de estos son los, cuadros de depreciación (si difiere de lo establecido en el Art. 30 de la Ley del Impuesto Sobre la Renta). Por lo que, el hecho de adoptar un nuevo marco de referencia para la información financiera, más que traer implicaciones tributarias que beneficien o no a la entidad a través de la forma en la que esta paga sus impuestos, se ven más reflejados en los beneficios que trae consigo la adopción de la normativa técnica como marco de referencia, ya que el hecho de que la información presentada en los estados financieros de la entidad puedan ser comparados trae seguridad al inversionista, además, de generar mejor información para la toma de decisiones de forma eficiente y oportuna. Sin embargo, aunque las entidades seguirán cumpliendo la legislación local, independientemente del marco de referencia para la presentación de información financiera, la entidad que decida adoptar las Normas Internacionales de Información Financiera para Pequeñas y Medianas Entidades (NIIF para las PYMES), debe tener en cuenta la forma en la que conciliara la información presentada con base en las NIIF para las PYMES con las disposiciones de la legislación tributaria local. Esto se hace a través de los hechos económicos registrados siguiendo la base técnica que generan diferencia con lo que la legislación tributaria local permite o exige; por lo que el Contador Público debe llevar un control especifico sobre cada una de estas diferencias, para poder realizar al final del ejercicio una conciliación que permita que la información presentada obtenga los beneficios asociados a su comparabilidad, confiabilidad y eficiencia a través del cumplimiento de la normativa técnica y que esta información no sea objeto de llamados de atención por parte de la Administración Tributaria

Mapping the human genetic architecture of COVID-19

We thank the entire COVID-19 HGI community for their contributions and continued collaboration. The work of the contributing studies was supported by numerous grants from governmental and charitable bodies. Acknowledgements specific to contributing studies are provided in Supplementary Table 13. We thank G. Butler-Laporte, G. Wojcik, M.-G. Hollm-Delgado, C. Willer and G. Davey Smith for their extensive feedback and discussion.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 diseases3–7. 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

Mapping the human genetic architecture of COVID-19

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