Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).
In India, often referred to as the "diabetes capital of the world," it is imperative to establish the level of knowledge among Asian Indians of Type 2 Diabetes (DM2) in order to plan effective public health programs aimed at prevention of DM2. Using an original survey of 983 college students in Visakhapatnam, Andhra Pradesh, we evaluated individuals' knowledge of DM2 including prevalence, risk factors, and prevention. To date, there are only a few studies that look at awareness of diabetes on the community level, and no previous studies have involved sampling college students. Our findings show that although awareness of diabetes is high, only half of the students sampled were aware that DM2 could be prevented and 60% were unaware that little or no exercise was a risk factor. The results suggest that diabetes awareness programs are needed among the college age population in India to prevent DM2.
In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.
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