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BACKGROUND:Several social indicators have been used in epidemiological research to describe socioeconomic position (SEP) of people in societies. Among SEP indicators, those more frequently used are education, occupational class and income. Differences in the incidence of several health outcomes have been reported consistently, independently from the indicator employed. Main objectives of the study were to present the socioeconomic classifications of the social indicators which will be employed throughout the LIFEPATH project and to compare social gradients in all-cause mortality observed in the participating adult cohorts using the different SEP indicators. METHODS:Information on the available social indicators (education, own and father's occupational class, income) from eleven adult cohorts participating in LIFEPATH was collected and harmonized. Mortality by SEP for each indicator was estimated by Poisson regression on each cohort and then evaluated using a meta-analytical approach. RESULTS:In the meta-analysis, among men mortality was significantly inversely associated with both occupational class and education, but not with father's occupational class; among women, the increase in mortality in lower social strata was smaller than among men and, except for a slight increase in the lowest education category, no significant differences were found. CONCLUSIONS:Among men, the proposed three-level classifications of occupational class and education were found to predict differences in mortality which is consistent with previous research. Results on women suggest that classifying them through their sole SEP, without considering that of their partners, may imply a misclassification of their social position leading to attenuation of mortality differences.

Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner's-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS. Further, as a way to incorporate external functional/annotation knowledge that could identify subsets of SNPs highly enriched for associations, we propose variable thresholds for SNPs selection. We applied our methods to GWAS summary-level data of 14 complex diseases. Across all diseases, a simple winner's curse correction uniformly led to enhancement of performance of the models, whereas incorporation of functional SNPs was beneficial only for selected diseases. Compared to the standard PRS algorithm, the proposed methods in combination led to notable gain in efficiency (25-50% increase in the prediction R2) for 5 of 14 diseases. As an example, for GWAS of type 2 diabetes, winner's curse correction improved prediction R2 from 2.29% based on the standard PRS to 3.10% (P = 0.0017) and incorporating functional annotation data further improved R2 to 3.53% (P = 2×10-5). Our simulation studies illustrate why differential treatment of certain categories of functional SNPs, even when shown to be highly enriched for GWAS-heritability, does not lead to proportionate improvement in genetic risk-prediction because of non-uniform linkage disequilibrium structure.

ABSTRACT A 2-year longitudinal microbiome study of 22 patients who underwent colectomy with an ileal pouch anal anastomosis detected significant increases in distinct populations of Bacteroides during 9 of 11 patient visits that coincided with inflammation (pouchitis). Oligotyping and metagenomic short-read annotation identified Bacteroides populations that occurred in early samples, bloomed during inflammation, and reappeared after antibiotic treatment. Targeted cultivation of Bacteroides isolates from the same individual at multiple time points and from several patients detected subtle genomic changes, including the identification of rapidly evolving genomic elements that differentiate isogenic strains of Bacteroides fragilis from the mucosa versus lumen. Each patient harbored Bacteroides spp. that are closely related to commonly occurring clinical isolates, including Bacteroides ovatus, B. thetaiotaomicron, B. vulgatus, and B. fragilis, which contained unique loci in different patients for synthesis of capsular polysaccharides. The presence of unique Bacteroides capsular polysaccharide loci within different hosts and between the lumen and mucosa may represent adaptations to stimulate, suppress, and evade host-specific immune responses at different microsites of the ileal pouch. IMPORTANCE This longitudinal study provides an opportunity to describe shifts in the microbiomes of individual patients who suffer from ulcerative colitis (UC) prior to and following inflammation. Pouchitis serves as a model for UC with a predictable incidence of disease onset and enables prospective longitudinal investigations of UC etiology prior to inflammation. Because of insufficient criteria for predicting which patients will develop UC or pouchitis, the interpretation of cross-sectional study designs suffers from lack of information about the microbiome structure and host gene expression patterns that directly correlate with the onset of disease. Our unique longitudinal study design allows each patient to serve as their own control, providing information about the state of the microbiome and host prior to and during the course of disease. Of significance to the broader community, this study identifies microbial strains that may have genetic elements that trigger the onset of disease in susceptible hosts.

BackgroundObesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.Methods and findingsThe association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of ConclusionsThese results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

In 2005, the World Health Organization set a global goal to reduce the rate of death from chronic (noncommunicable) disease by an additional 2% every year. A major component in this strategy was a reduction in the use of tobacco products, as described in the World Health Organization Framework Convention on Tobacco Control. According to recent estimates, over 10 yrs (2006–2015) 13.8 million deaths could be averted by the implementation of such interventions, at a cost of less than US$0.40 person–1·yr–1 in low-income and lower middle-income countries, and US$0.50–1.00 person–1·yr–1 in upper middle-income countries. According to estimates, approximately one third of tobacco-related deaths will be due to respiratory causes, one third to cancer and one third to cardiovascular diseases. Most of the burden of tobacco in the future will be in low-income countries.

Antarctica polynyas support intense phytoplankton blooms, impacting their environment by a substantial depletion of inorganic carbon and nutrients. These blooms are dominated by the colony-forming haptophyte Phaeocystis antarctica and they are accompanied by a distinct bacterial population. Yet, the ecological role these bacteria may play in P. antarctica blooms awaits elucidation of their functional gene pool and of the geochemical activities they support. Here, we report on a metagenome (῀160 million reads) analysis of the microbial community associated with a P. antarctica bloom event in the Amundsen Sea polynya (West Antarctica). Genomes of the most abundant Bacteroidetes and Proteobacteria populations have been reconstructed and a network analysis indicates a strong functional partitioning of these bacterial taxa. Three of them (SAR92, and members of the Oceanospirillaceae and Cryomorphaceae) are found in close association with P. antarctica colonies. Distinct features of their carbohydrate, nitrogen, sulfur and iron metabolisms may serve to support mutualistic relationships with P. antarctica. The SAR92 genome indicates a specialization in the degradation of fatty acids and dimethylsulfoniopropionate (compounds released by P. antarctica) into dimethyl sulfide, an aerosol precursor. The Oceanospirillaceae genome carries genes that may enhance algal physiology (cobalamin synthesis). Finally, the Cryomorphaceae genome is enriched in genes that function in cell or colony invasion. A novel pico-eukaryote, Micromonas related genome (19.6 Mb, ~94% completion) was also recovered. It contains the gene for an anti-freeze protein, which is lacking in Micromonas at lower latitudes. These draft genomes are representative for abundant microbial taxa across the Southern Ocean surface.

Advances in high-throughput sequencing and ‘omics technologies are revolutionizing studies of naturally occurring microbial communities. Comprehensive investigations of microbial lifestyles require the ability to interactively organize and visualize genetic information and to incorporate subtle differences that enable greater resolution of complex data. Here we introduce anvi’o, an advanced analysis and visualization platform that offers automated and human-guided characterization of microbial genomes in metagenomic assemblies, with interactive interfaces that can link ‘omics data from multiple sources into a single, intuitive display. Its extensible visualization approach distills multiple dimensions of information about each contig, offering a dynamic and unified work environment for data exploration, manipulation, and reporting. Using anvi’o, we re-analyzed publicly available datasets and explored temporal genomic changes within naturally occurring microbial populations through de novo characterization of single nucleotide variations, and linked cultivar and single-cell genomes with metagenomic and metatranscriptomic data. Anvi’o is an open-source platform that empowers researchers without extensive bioinformatics skills to perform and communicate in-depth analyses on large ‘omics datasets.

ABSTRACT Molecular characterizations of the gut microbiome from individual human stool samples have identified community patterns that correlate with age, disease, diet, and other human characteristics, but resources for marker gene studies that consider microbiome trends among human populations scale with the number of individuals sampled from each population. As an alternative strategy for sampling populations, we examined whether sewage accurately reflects the microbial community of a mixture of stool samples. We used oligotyping of high-throughput 16S rRNA gene sequence data to compare the bacterial distribution in a stool data set to a sewage influent data set from 71 U.S. cities. On average, only 15% of sewage sample sequence reads were attributed to human fecal origin, but sewage recaptured most (97%) human fecal oligotypes. The most common oligotypes in stool matched the most common and abundant in sewage. After informatically separating sequences of human fecal origin, sewage samples exhibited ~3× greater diversity than stool samples. Comparisons among municipal sewage communities revealed the ubiquitous and abundant occurrence of 27 human fecal oligotypes, representing an apparent core set of organisms in U.S. populations. The fecal community variability among U.S. populations was significantly lower than among individuals. It clustered into three primary community structures distinguished by oligotypes from either: Bacteroidaceae, Prevotellaceae, or Lachnospiraceae/Ruminococcaceae. These distribution patterns reflected human population variation and predicted whether samples represented lean or obese populations with 81 to 89% accuracy. Our findings demonstrate that sewage represents the fecal microbial community of human populations and captures population-level traits of the human microbiome. IMPORTANCE The gut microbiota serves important functions in healthy humans. Numerous projects aim to define a healthy gut microbiome and its association with health states. However, financial considerations and privacy concerns limit the number of individuals who can be screened. By analyzing sewage from 71 cities, we demonstrate that geographically distributed U.S. populations share a small set of bacteria whose members represent various common community states within U.S. adults. Cities were differentiated by their sewage bacterial communities, and the community structures were good predictors of a city's estimated level of obesity. Our approach demonstrates the use of sewage as a means to sample the fecal microbiota from millions of people and its potential to elucidate microbiome patterns associated with human demographics.

The relationship between coffee consumption and coronary heart disease (CHD) has been investigated in several studies with discrepant results. We examined the association between Italian-style (espresso and mocha) coffee consumption and CHD risk.We investigated 12,800 men and 30,449 women without history of cardiovascular disease recruited to the EPICOR prospective cohort study. Coffee consumption was assessed at baseline. In a random sub-cohort of 1472 subjects, plasma triglycerides, and total, LDL and HDL cholesterol were determined to investigate the effect of coffee consumption on plasma lipids.After a mean follow up of 10.9 years, 804 cases of CHD (500 acute events, 56 fatal events and 248 revascularizations, all first events) were identified. Multivariable adjusted hazard ratios for CHD were: 1.18 (95% CI 0.87-1.60) for drinking 1-2 cups/day, 1.37 (95% CI 1.03-1.82) for >2-4 cups/day and 1.52 (95% CI 1.11-2.07) for over 4 cups/day (P trend

BACKGROUND:Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS:Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. RESULTS:In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend

Although metabolic profiles have been associated with chronic disease risk, lack of temporal stability of metabolite levels could limit their use in epidemiological investigations. The present study aims to evaluate the reliability over a two-year period of 158 metabolites and compare reliability over time in fasting and non-fasting serum samples.Metabolites were measured with the AbsolueIDQp180 kit (Biocrates, Innsbruck, Austria) by mass spectrometry and included acylcarnitines, amino acids, biogenic amines, hexoses, phosphatidylcholines and sphingomyelins. Measurements were performed on repeat serum samples collected two years apart in 27 fasting men from Turin, Italy, and 39 non-fasting women from Utrecht, The Netherlands, all participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Reproducibility was assessed by estimating intraclass correlation coefficients (ICCs) in multivariable mixed models.In fasting samples, a median ICC of 0.70 was observed. ICC values were 0.50 in fasting and non-fasting samples, respectively. ICCs were higher in fasting samples that are preferable to non-fasting.

Background: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand whether the observed associations might be partially explained by lifestyle behaviors. Methods: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level [measured through the Relative Index of Inequality (RII)] on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). Results: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared with more educated participants. Mediation analyses showed that portions of the TE of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). Conclusions: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. Impact: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population. [ABSTRACT FROM AUTHOR]

Higher consumption of ultra-processed foods (UPF) has been associated with childhood obesity, but underlying mechanisms remain unclear. We investigated plasma nuclear magnetic resonance metabolic profiles of higher UPF consumption and their role in obesity risk in the British ALSPAC cohort. We performed cross-sectional and prospective metabolome wide association analyses of UPF, calculated from food diaries using the NOVA classification. In cross-sectional analysis, we tested the association between UPF consumption and metabolic profile at 7 years (N = 4528), and in the prospective analysis we tested the association between UPF consumption at 13 years and metabolic profile at 17 years (N = 3086). Effects of UPF-associated metabolites at 7 years on subsequent fat mass accumulation were assessed using growth curve models. At 7 years, UPF was associated with 115 metabolic traits including lower levels of branched-chain and aromatic amino acids and higher levels of citrate, glutamine, and monounsaturated fatty acids, which were also associated with greater fat mass accumulation. Reported intake of nutrients mediated associations with most metabolites, except for citrate. UPF consumption among British children is associated with perturbation of multiple metabolic traits, many of which contribute to child obesity risk. [ABSTRACT FROM AUTHOR]