Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10−8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10−5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15–0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1–0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈−0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 x 10(-8)), while five of the 21 lead SNPs reach suggestive significance (P < 1 x 10(-5)) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (r(g) approximate to 0.15-0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|r(g)| approximate to 0.1-0.3) and positive genetic correlations with physical activity (r(g) approximate to 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (r(g) approximate to-0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.Public Health and primary carePrevention, Population and Disease management (PrePoD

Role of miR-2392 in driving SARS-CoV-2 infection

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans

Analysis of Weapons-Grade MOX VVER-1000 Benchmarks with HELIOS and KENO

Calculations of computational benchmark problems for the disposition of weapons-grade mixed-oxide fuel in VVER-1000 reactors have been performed with the HELIOS fuel assembly analysis code. The benchmarks cover pin cell, single fuel assembly, and multiassembly structures with several different fuel types, moderator densities, and boron content for operational and off-normal conditions. Fuel depletion is performed to a burnup of 60 MWd/kg. The detailed results have been tabulated for multiplication factors, macroscopic and microscopic cross sections, reaction rates, fuel isotopics, and fission distributions. Additional results are given for a preliminary analysis of a multiassembly variant using the KENO Monte Carlo code with cross sections from HELIOS

Comparison of waist circumference percentiles versus body mass index percentiles for diagnosis of excessive fatness in a large cohort of children

Context. Waist circumference may offer improved diagnosis of obesity in youth compared with body mass index (BMI), but empirical evidence is limited. Objective. To compare the ability of BMI percentile using UK reference data and waist circumference percentile using UK reference data to diagnose high fat mass in English children. Design and Methods. In 7 722 9–10-year-olds (3 809 boys, 3 913 girls) sensitivity and specificity were calculated and receiver operator characteristic (ROC) analyses undertaken to determine the diagnostic accuracy of BMI and waist circumference z-scores to define high fat mass measured by dual energy x-ray absorptiometry (DXA). High fat mass was defined as being in the top decile of fatness for each sex (359 boys and 367 girls). Results. The area under the ROC curve was slightly higher for BMI percentile (0.92 in boys, 95% CI: 0.91 –0.93; 0.94 in girls, 95% CI: 0.93–0.95) than waist circumference percentile (0.89 in boys, 95% CI: 0.86–0.91; 0.81 in girls, 95% CI: 0.73–0.90). Specificity of BMI percentile was slightly but significantly higher than that of waist circumference percentile for both sexes (p<0.05 in each case). Conclusions. The present study suggests that waist circumference percentile has no advantage over BMI percentile for the diagnosis of high fat mass in children

Progression from childhood overweight to adolescent obesity in a large contemporary cohort

The overweight - as distinct from obese - child is a potential target for obesity prevention interventions, on the assumption that overweight often progresses to obesity. However, there is limited empirical evidence on the probability that overweight progresses to obesity in contemporary children. To quantify progression from overweight to obesity in a large contemporary cohort of children. Changes in weight status were studied longitudinally in 7-year-olds (n=5 175) participating in the Avon Longitudinal Study of Parents and Children (ALSPAC), over a 6-year period. Obesity was defined as BMI z-score ≥1.64 and overweight defined as BMI z-score ≥1.04 but <1.64. Adjusted odds ratio for progression to obesity at age 13 for overweight at age 7 was 18.1 (95% CI 12.8-25.6), and 34% of overweight children at age 7 became obese by age 13 years. The present study could inform judgements as to the value of monitoring changes in weight status in overweight children, and the extent to which the overweight state might be a useful target of future obesity prevention interventions

Habitats of small pelagic fish

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