Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.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

A first update on mapping the human genetic architecture of COVID-19

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Balanced dynamics of deep and shallow Hadley circulations in the tropics

Artículo científico -- Universidad de Costa Rica. Centro de Investigaciones Geofísicas, 2014This paper examines the dynamics of large-scale overturning circulations in the tropical atmosphere using an idealized zonally symmetric model on the equatorial b-plane. Under certain simplifications of its coefficients, the elliptic partial differential equation for the transverse circulation can be solved by first performing a vertical transform to obtain a horizontal structure equation, and then using Green’s function to solve the horizontal structure equation. When deep diabatic heating is present in the Intertropical Convergence Zone (ITCZ), the deep Hadley circulation is of first-order importance. In the absence of deep diabatic heating, the interior circulation associated with Ekman pumping cannot penetrate deep into the troposphere because the resistance of fluid parcels to horizontal motion (i.e., inertial stability) is significantly smaller than their resistance to vertical motion (i.e., static stability). In this scenario, only a shallow Hadley circulation exists. The shallow overturning circulation is characterized by meridional velocities as large as 7 m s21 at the top of the boundary layer, in qualitative agreement with observations in the tropical eastern Pacific. The meridional asymmetry between the winter and summer deep and shallow Hadley cells is attributed to the anisotropy of the inertial stability parameter, and as the ITCZ widens meridionally or as the forcing involves higher vertical wave numbers, the asymmetry between the winter and summer cells increases.Universidad de Costa Rica, Centro de Investigaciones GeofísicasUniversidad de Costa Rica, Escuela de FísicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI