Data_Sheet_1_Genetically high angiotensin-converting enzyme concentrations causally increase asthma risk: A meta-analysis using Mendelian randomization.PDF

ObjectivesThis meta-analysis aimed to test the association of angiotensin-converting enzyme (ACE) gene I/D polymorphism with asthma risk and circulating ACE changes.MethodsPublic literature retrieval, publication selection, and information extraction were completed independently by two investigators. Effect-size values are expressed as odds ratios (ORs) or standardized mean differences (SMDs) with a 95% confidence interval (95% CI).ResultsNineteen studies (2,888 patients and 9,549 controls) fulfilled the eligibility criteria. Overall investigations demonstrated that ACE gene I/D polymorphism was significantly associated with asthma risk under allelic (OR, 95% CI: 1.26, 1.08 to 1.48), homozygous genotypic (1.50, 1.09 to 2.06), and recessive (1.53, 1.24 to 1.89) models with moderate heterogeneity (I2 statistic: 64% to 79%). Subsidiary investigations recorded that race, matched status, asthma diagnosis, sample size, and age possibly accounted for the existence of significant heterogeneity. Relative to carriers with the II genotype, those with the DD genotype, ID genotype, and the combination of DD and ID genotypes had significantly higher concentrations of circulating ACE (WMD: 3.13, 2.07, and 2.83 U/L, respectively, p ConclusionWe provided strong meta-analytical evidence supporting the causal implication of high circulating ACE concentrations in the development of asthma.</p

Additional file 1: Figure S1. of X chromosome-wide analysis identifies DNA methylation sites influenced by cigarette smoking

Distribution of mean β-values of all X chromosomal sites in males (A) and females (B). Figure S2. Quantile-quantile plot comparing observed p-values to expected p-values of all CpG sites on the X chromosome from the epigenetic association study with current smoking status. Dashed line indicates 95 % CI for distribution of expected p-values. Figure S3. Manhattan plot of all CpG sites on the X chromosome and their association with current smoking status. The red line represents a FDR significance level of 0.05. Figure S4. Forest plots of the smoking-related DNAm sites in males from the discovery and three replication samples using M-value. A: cg07764473 (BCOR). B: cg21380860 (TSC22D3). (PDF 703 kb

Polymorphisms in the vitamin D receptor gene are associated with reduced rate of sputum culture conversion in multidrug-resistant tuberculosis patients in South Africa

<div><p>Background</p><p>Vitamin D modulates the inflammatory and immune response to tuberculosis (TB) and also mediates the induction of the antimicrobial peptide cathelicidin. Deficiency of 25-hydroxyvitamin D and single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk of TB disease and decrease culture conversion rates in drug susceptible TB. Whether these VDR SNPs are found in African populations or impact multidrug-resistant (MDR) TB treatment has not been established. We aimed to determine if SNPs in the VDR gene were associated with sputum culture conversion among a cohort of MDR TB patients in South Africa.</p><p>Methods</p><p>We conducted a prospective cohort study of adult MDR TB patients receiving second-line TB treatment in KwaZulu-Natal province. Subjects had monthly sputum cultures performed. In a subset of participants, whole blood samples were obtained for genomic analyses. Genomic DNA was extracted and genotyped with Affymetrix Axiom Pan-African Array. Cox proportional models were used to determine the association between VDR SNPs and rate of culture conversion.</p><p>Results</p><p>Genomic analyses were performed on 91 MDR TB subjects enrolled in the sub-study; 60% were female and median age was 35 years (interquartile range [IQR] 29–42). Smoking was reported by 21% of subjects and most subjects had HIV (80%), were smear negative (57%), and had cavitary disease (55%). Overall, 87 (96%) subjects initially converted cultures to negative, with median time to culture conversion of 57 days (IQR 17–114). Of 121 VDR SNPs examined, 10 were significantly associated (p<0.01) with rate of sputum conversion in multivariable analyses. Each additional risk allele on SNP rs74085240 delayed culture conversion significantly (adjusted hazard ratio 0.30, 95% confidence interval 0.14–0.67).</p><p>Conclusions</p><p>Polymorphisms in the VDR gene were associated with rate of sputum culture conversion in MDR TB patients in this high HIV prevalence setting in South Africa.</p></div

Poor tuberculosis treatment outcome by vitamin D receptor gene single nucleotide polymorphism, N = 88.

<p>Poor tuberculosis treatment outcome by vitamin D receptor gene single nucleotide polymorphism, N = 88.</p

Baseline participant characteristics and 2-month sputum culture status.

<p>Baseline participant characteristics and 2-month sputum culture status.</p

Principal component analysis of study participants compared to HapMap ethnic groups.

<p>Principal component analysis of study participants compared to HapMap ethnic groups.</p

Hazard of sputum culture conversion by vitamin D receptor gene single nucleotide polymorphism.

<p>Hazard of sputum culture conversion by vitamin D receptor gene single nucleotide polymorphism.</p

Enrichment for functional annotations and cell-type groups using stratified LD score regression.

<p><b>A.</b> Enrichment estimates of 24 main annotations for each of four BP traits. Annotations are ordered by size. Error bars represent jackknife standard errors around the estimates of enrichment, and stars indicate significance at P < 0.05 after Bonferroni correction for 24 hypotheses tested and four BP traits. <b>B.</b> Significance of enrichment of 10 cell-type groups for four BP traits. Dotted line and stars indicate significance at P < 0.05 after Bonferroni correction for 10 hypotheses tested and four BP traits.</p

Intelligent Forecasting of Electricity Demand

In this paper, a number of approaches to the modelling of electricity demand, on a variety of time-scales, are considered. These approaches fall under the category of 'intelligent' systems engineering, where techniques such as neural networks, fuzzy logic and genetic algorithms are employed. The paper attempts to give some motivation for the employment of such techniques, while also making some effort to be realistic about the limitations of such methods, in particular a number of important caveats that should be borne in mind when utilising these techniques within the current application domain. In general, the electricity demand data is modelled as a time series, but one application considered involves application of linguistic modelling to capture operator expertise

Relative renal mRNA levels of genes identified at baseline and after 2 weeks of Ang II-induced hypertension.

<p><i>HPRT</i> gene was used for normalization. N ≥ 5 in each group. <b>A.</b> Genes that were differentially expressed between baseline and Ang II conditions. <b>B.</b> Genes that were not altered between the two conditions. * P < 0.05. ** P < 0.01. *** P < 0.001.</p