Molecular models of tissue-dependent <i>cis</i>-regulation.

<p>The observed tissue-dependent <i>cis</i>-regulations can be explained by two molecular models: (A) the tissue-dependent use of the same causal variants, or (B) the use of tissue-dependent causal variants. The ovals indicate the two regulatory factors (e.g., transcription factors) that play regulatory roles in different tissues (brown in tissue 1 and purple in tissue 2). These factors can recognize the same or different <i>cis</i>-elements (the yellow region). The genetic variants are shown as SNPs with A/G alleles. The SNPs in red are causal variants and the SNPs in blue are tag SNPs. The red line between them indicates the linkage disequilibrium. The arrows indicate the effect of regulatory factors, here the up arrows represent expression stimulators and the down arrows expression suppressors. The size of the arrows indicates the size of the differences between the expression of A and G alleles, i.e., the <i>cis</i>-eQTL effect size.</p

<i>cis</i>-regulation of gene expression between tissues.

<p>The associated probe-SNP pairs were classified to be concordant <i>or</i> discordant between tissues. The small pie plot shows the proportion of probes that have only concordant <i>association</i> (red part) or at least one discordant association (blue part). The probes with discordant association were under tissue-dependent regulation and we characterized four different mechanisms: specific regulation, alternative regulation, different effect size and opposite effect sizes. Their proportions are shown in the large blue pie plot. The concordant <i>cis</i>-regulation and the four different mechanisms are illustrated by the correlation between SNP genotypes (AA, AG and GG) and gene expression levels in two tissues: brown dots represent the expression of a gene in tissue 1 and purple dots the expression of a gene in tissue 2.</p

COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19

The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p