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

peer reviewe

Interleukin-16 (IL-16) Gene Polymorphisms in Iranian Patients with Colorectal Cancer

Abstract Background & Aims: A number of theories have been put forward to clarify the etiology of colorectal cancer (CRC), such as genetic alterations and cytokine production. A combination of inflammatory cytokines has an important role in cancer development. The aim of our study was to screen for alterations located in promoter and exons of IL-16 gene sequence, to determine the distribution of genotypes in individuals with CRC and healthy controls in a sample of Iranian population. methods: The case group consisted of 260 individuals with colorectal cancer and the control group included 405 healthy individuals. Three IL-16 gene polymorphisms (rs4072111, rs11556218, rs4778889) were genotyped using PCR-RFLP method. RFLP results were confirmed by direct sequencing. Results: A significant association between rs11556218 SNP in the IL-16 gene and the risk of CRC was found. The TG genotype of rs11556218 T/G polymorphism showed significant association with a 1.75 fold increased risk of CRC (P=0.005; adjusted OR: 1.759; 95% CI: 1.191-2.598). In addition a significant association between CC genotype of rs4778889 T/C polymorphism and decreased risk of CRC in male subjects (P=0.045; adjusted OR: 0.192; 95% CI: 0.038-0.967) was determined. Conclusion: This study is the first report of IL-16 gene polymorphisms among CRC patients from Iran. Our results suggest an influence of rs11556218 T>G and rs4778889 T/C polymorphisms on the altered risk of CRC

Iranian Hepatitis C, chronic Transforming Growth Factor Beta1

Background: Chronic hepatitis C infection is caused by the hepatitis C virus (HCV), and its clinical complications include liver cirrhosis, liver failure, and hepatocellular carcinoma. Transforming growth factor-β1 (TGF-β1) is an important cytokine in cell growth and differentiation, angiogenesis, extracellular matrix formation, immune response regulation, and cancer development and progression. Objectives: The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in TGF-β1 and chronic HCV infection among patients referred to the Taleghani Hospital, Tehran, Iran between 2008 and 2010. Patients and Methods: In this case-control study, samples were collected using a convenience sampling method. We genotyped 164 HCV patients and 169 healthy controls for 3 SNPs in the TGF-β1 gene (-509 promoter, codon 10, and codon 25). We determined the SNP genotypes by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. To confirm the PCR-RFLP genotyping results, 10 % of the samples were re-genotyped using a direct sequencing method