Appropriate waist circumference cut points for identifying insulin resistance in black youth: a cross sectional analysis of the 1986 Jamaica birth cohort

Background While the International Diabetes Federation (IDF) has ethnic specific waist circumference (WC) cut-points for the metabolic syndrome for Asian populations it is not known whether the cut-points for black populations should differ from those for European populations. We examined the validity of IDF WC cut points for identifying insulin resistance (IR), the underlying cause of the metabolic syndrome, in predominantly black, young Jamaican adults. Methods Participants from a 1986 birth cohort were evaluated between 2005 and 2007 when they were 18-20 years old. Trained observers took anthropometric measurements and collected a fasting blood sample. IR was assessed using the homeostasis model assessment computer programme (HOMA-IR). Sex specific quartiles for IR were generated using HOMA-IR values and participants in the highest quartile were classified as "insulin resistant". Receiver operator characteristic (ROC) curves were used to estimate the best WC to identify insulin resistance. The sensitivity and specificity of these values were compared with the IDF recommended WC cut-points. Results Data from 707 participants (315 males; 392females) were analysed. In both sexes those with IR were more obese, had higher mean systolic blood pressure, glucose and triglycerides and lower mean HDL cholesterol. The WC was a good predictor of IR with an ROC area under the curve (95% CI) of 0.71(0.64,0.79) for men and 0.72(0.65,0.79) for women. Using the Youden Index (J) the best WC cut point for identifying IR in male participants was 82 cm (sensitivity 45%, specificity 93%, J 0.38) while the standard cut point of 94 cm had a sensitivity of 14% and specificity of 98% (J 0.12). In the female participants 82 cm was also a good cut point for identifying IR (sensitivity 52%, specificity 87%, J 0.39) and was similar to the standard IDF 80 cm cut point (sensitivity 53%, specificity 82%, J 0.35). Conclusions The WC that identified IR in young black men is lower than the IDF recommended WC cut point. Sex differences in WC cut points for identifying IR were less marked in this population than in other ethnic groups

Investigating the causal relationship of c-reactive protein with 32 complex somatic and psychiatric outcomes: a large-scale cross-consortium mendelian randomization study

BackgroundC-reactive protein (CRP) is associated with immune, cardiometabolic, and psychiatric traits and diseases. Yet it is inconclusive whether these associations are causal. Methods and FindingsWe performed Mendelian randomization (MR) analyses using two genetic risk scores (GRSs) as instrumental variables (IVs). The first GRS consisted of four single nucleotide polymorphisms (SNPs) in the CRP gene (GRSCRP), and the second consisted of 18 SNPs that were significantly associated with CRP levels in the largest genome-wide association study (GWAS) to date (GRSGWAS). To optimize power, we used summary statistics from GWAS consortia and tested the association of these two GRSs with 32 complex somatic and psychiatric outcomes, with up to 123,865 participants per outcome from populations of European ancestry. We performed heterogeneity tests to disentangle the pleiotropic effect of IVs. A Bonferroni-corrected significance level of less than 0.0016 was considered statistically significant. An observed p-value equal to or less than 0.05 was considered nominally significant evidence for a potential causal association, yet to be confirmed. The strengths (F-statistics) of the IVs were 31.92–3,761.29 and 82.32–9,403.21 for GRSCRP and GRSGWAS, respectively. CRP GRSGWAS showed a statistically significant protective relationship of a 10% genetically elevated CRP level with the risk of schizophrenia (odds ratio [OR] 0.86 [95% CI 0.79–0.94]; p < 0.001). We validated this finding with individual-level genotype data from the schizophrenia GWAS (OR 0.96 [95% CI 0.94–0.98]; p < 1.72 × 10−6). Further, we found that a standardized CRP polygenic risk score (CRPPRS) at p-value thresholds of 1 × 10−4, 0.001, 0.01, 0.05, and 0.1 using individual-level data also showed a protective effect (OR < 1.00) against schizophrenia; the first CRPPRS (built of SNPs with p < 1 × 10−4) showed a statistically significant (p < 2.45 × 10−4) protective effect with an OR of 0.97 (95% CI 0.95–0.99). The CRP GRSGWAS showed that a 10% increase in genetically determined CRP level was significantly associated with coronary artery disease (OR 0.88 [95% CI 0.84–0.94]; p < 2.4 × 10−5) and was nominally associated with the risk of inflammatory bowel disease (OR 0.85 [95% CI 0.74–0.98]; p < 0.03), Crohn disease (OR 0.81 [95% CI 0.70–0.94]; p < 0.005), psoriatic arthritis (OR 1.36 [95% CI 1.00–1.84]; p < 0.049), knee osteoarthritis (OR 1.17 [95% CI 1.01–1.36]; p < 0.04), and bipolar disorder (OR 1.21 [95% CI 1.05–1.40]; p < 0.007) and with an increase of 0.72 (95% CI 0.11–1.34; p < 0.02) mm Hg in systolic blood pressure, 0.45 (95% CI 0.06–0.84; p < 0.02) mm Hg in diastolic blood pressure, 0.01 ml/min/1.73 m2 (95% CI 0.003–0.02; p < 0.005) in estimated glomerular filtration rate from serum creatinine, 0.01 g/dl (95% CI 0.0004–0.02; p < 0.04) in serum albumin level, and 0.03 g/dl (95% CI 0.008–0.05; p < 0.009) in serum protein level. However, after adjustment for heterogeneity, neither GRS showed a significant effect of CRP level (at p < 0.0016) on any of these outcomes, including coronary artery disease, nor on the other 20 complex outcomes studied. Our study has two potential limitations: the limited variance explained by our genetic instruments modeling CRP levels in blood and the unobserved bias introduced by the use of summary statistics in our MR analyses. ConclusionsGenetically elevated CRP levels showed a significant potentially protective causal relationship with risk of schizophrenia. We observed nominal evidence at an observed p < 0.05 using either GRSCRP or GRSGWAS—with persistence after correction for heterogeneity—for a causal relationship of elevated CRP levels with psoriatic osteoarthritis, rheumatoid arthritis, knee osteoarthritis, systolic blood pressure, diastolic blood pressure, serum albumin, and bipolar disorder. These associations remain yet to be confirmed. We cannot verify any causal effect of CRP level on any of the other common somatic and neuropsychiatric outcomes investigated in the present study. This implies that interventions that lower CRP level are unlikely to result in decreased risk for the majority of common complex outcomes

Effects of Cu/Zn Superoxide Dismutase (sod1) Genotype and Genetic Background on Growth, Reproduction and Defense in Biomphalaria glabrata

Resistance of the snail Biomphalaria glabrata to the trematode Schistosoma mansoni is correlated with allelic variation at copper-zinc superoxide dismutase (sod1). We tested whether there is a fitness cost associated with carrying the most resistant allele in three outbred laboratory populations of snails. These three populations were derived from the same base population, but differed in average resistance. Under controlled laboratory conditions we found no cost of carrying the most resistant allele in terms of fecundity, and a possible advantage in terms of growth and mortality. These results suggest that it might be possible to drive resistant alleles of sod1 into natural populations of the snail vector for the purpose of controlling transmission of S. mansoni. However, we did observe a strong effect of genetic background on the association between sod1 genotype and resistance. sod1 genotype explained substantial variance in resistance among individuals in the most resistant genetic background, but had little effect in the least resistant genetic background. Thus, epistatic interactions with other loci may be as important a consideration as costs of resistance in the use of sod1 for vector manipulation

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

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

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood

The burden and determinants of complications and comorbidities in contemporary youth-onset diabetes are unknown