Additional file 1: of The genetics of smoking in individuals with chronic obstructive pulmonary disease

Supplementary Figures and Tables. (DOCX 1183 kb

An IL-13 Promoter Polymorphism Associated with Liver Fibrosis in Patients with <i>Schistosoma japonicum</i>

<div><p>The aim of this study was to determine whether two polymorphisms in the gene encoding <i>IL13</i> previously associated with <i>Schistosoma hematobium</i> (<i>S</i>. <i>hematobium</i>) and <i>S</i>. <i>mansoni</i> infection are associated with <i>S</i>. <i>japonicum</i> infection. Single nucleotide polymorphisms (SNPs) rs1800925 (IL13/-1112C>T) and rs20541 (IL13R130Q) were genotyped in 947 unrelated individuals (307 chronically infected, 339 late-stage with liver fibrosis, 301 uninfected controls) from a schistosomiasis-endemic area of Hubei province in China. Regression models were used to evaluate allelic and haplotypic associations with chronic and late-stage schistosomiasis adjusted for non-genetic covariates. Expression of IL-13 was measured in <i>S</i>. <i>japonicun</i>-infected liver fibrosis tissue and normal liver tissue from uninfected controls by immunohistochemistry (IHC). The role of rs1800925 in IL-13 transcription was further determined by Luciferase report assay using the recombinant PGL4.17-rs180092 plasmid. We found SNP rs1800925T was associated with late-stage schistosomiasis caused by <i>S</i>. <i>japonicum</i> but not chronic schistosomiasis (OR = 1.39, 95%CI = 1.02–1.91, p = 0.03) and uninfected controls (OR = 1.49, 95%CI = 1.03–2.13, p = 0.03). Moreover, the haplotype rs1800925T-rs20541C increased the risk of disease progression to late-stage schistosomiasis (OR = 1.46, p = 0.035), whereas haplotype rs1800925C-rs20541A showed a protective role against development of late-stage schistosomiasis (F = 0.188, OR = 0.61, p = 0.002). Furthermore, <i>S</i>. <i>japonicum</i>-induced fibrotic liver tissue had higher IL13 expression than normal liver tissue. Plasmid PGL4.17-rs1800925T showed a stronger relative luciferase activity than Plasmid PGL4.17-rs1800925C in 293FT, QSG-7701 and HL-7702 cell lines. In conclusion, the functional <i>IL13</i> polymorphism, rs1800925T, previously associated with risk of schistosomiasis, also contributes to risk of late-stage schistosomiasis caused by <i>S</i>. <i>japonicum</i>.</p></div

Haplotypic association of <i>IL13</i> SNPs with chronic and late-stage <i>S</i>. <i>japonicum</i> infection.

<p>F1, frequency of controls; F2, frequency of chronic cases; F3, frequency of late-stage cases.</p><p>Haplotypic association of <i>IL13</i> SNPs with chronic and late-stage <i>S</i>. <i>japonicum</i> infection.</p

Allelic association of <i>IL13</i> SNPs with chronic and late-stage <i>S</i>. <i>japonicum infection</i>.

<p>Allelic association of <i>IL13</i> SNPs with chronic and late-stage <i>S</i>. <i>japonicum infection</i>.</p

Relative luciferase activity of plasmid construct of PGL4.17-rs1800925T and PGL4.17-rs1800925C in 293FT, QSG-7701 and HL-7702 cell lines.

<p>(A) Complementary base sequence of target DNA in plasmid PGL4.17-rs1800925C. (B) Complementary base sequence of target DNA in plasmid PGL4.17-rs1800925T constructed by overlap PCR. (C) Relative luciferase activity of plasmid construct of PGL4.17-rs1800925T and PGL4.17-rs1800925C in 293FT, QSG-7701 and HL-7702 cell lines. (Rs1800925C indicates plasmid PGL4.17-rs1800925C and rs1800925T indicates plasmid PGL4.17-rs1800925T).</p

IL-13 protein was determined by IHC and western blot.

<p>(A) Representative images of normal liver tissues and <i>S</i>.<i>japonicum</i>-induced fibrotic liver tissues (Images were captured at 100x and 400x with scale bar of 100 μm). (B) Comparison of scores of ST2 staining intensity betwee <i>S</i>. <i>japonicum</i>-induced fibrotic liver tissues and normal liver tissues. (C) IL-13 protein was detected in liver tissue lysates by western blots.</p

General characteristics of <i>IL13</i> SNPs in Chines study samples.

<p>* From hg19.</p><p>General characteristics of <i>IL13</i> SNPs in Chines study samples.</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