Long Noncoding RNA TRIBAL Links the 8q24.13 Locus to Hepatic Lipid Metabolism and Coronary Artery Disease.

Background: Genome-wide association studies identified a 20-Kb region of chromosome 8 (8q24.13) associated with plasma lipids, hepatic steatosis, and risk for coronary artery disease. The region is proximal to , and given its well-established role in lipid regulation in animal models, TRIB1 has been proposed to mediate the contribution of the 8q24.

Multiomics Screening Identified CpG Sites and Genes That Mediate the Impact of Exposure to Environmental Chemicals on Cardiometabolic Traits.

An understanding of the molecular mechanism whereby an environmental chemical causes a disease is important for the purposes of future applications. In this study, a multiomics workflow was designed to combine several publicly available datasets in order to identify CpG sites and genes that mediate the impact of exposure to environmental chemicals on cardiometabolic traits. Organophosphate and prenatal lead exposure were previously reported to change methylation level at the cg23627948 site.

Multiomics Data Analysis Identified CpG Sites That Mediate the Impact of Smoking on Cardiometabolic Traits.

Understanding the epigenome paths through which smoking contributes to cardiometabolic traits is important for downstream applications. In this study, an SNP-based analytical pipeline was used to integrate several publicly available datasets in order to identify CpG sites that mediate the impact of smoking on cardiometabolic traits and to investigate the underlying molecular mechanisms. After applying stringent statistical criteria, 11 CpG sites were detected that showed significant association ( < 5 × 10) with cardiometabolic traits at both the discovery and replication stages.

Genome-wide search identified DNA methylation sites that regulate the metabolome.

Identifying DNA methylation sites that regulate the metabolome is important for several purposes. In this study, publicly available GWAS data were integrated to find methylation sites that impact metabolome through a discovery and replication scheme and by using Mendelian randomization. The outcome of analyses revealed 107 methylation sites associated with 84 metabolites at the genome-wide significance level (<5e) at both the discovery and replication stages.

Genome-wide screening identifies DNA methylation sites that regulate the blood proteome.

Identifying DNA methylation sites that regulate the blood proteome is important for biomedical purposes. Here the authors performed a genome-wide search to find DNA methylation sites that impact proteins.  The authors identified 165 methylation sites associated with 138 proteins.

Does the Presence of Type 2 Diabetes or Metabolic Syndrome Impact Reduction in Waist Circumference During Weight Loss?

Objectives: Our aim in this study was to compare the change in waist circumference given the same degree of weight loss in patients who meet the criteria for metabolic syndrome or type 2 diabetes and those who do not meet these criteria. Because visceral adiposity is a key feature of both conditions and intra-abdominal adipocytes show higher lipolytic activity, we sought to determine whether changes in waist circumference differed in individuals with and without these conditions.

Methods: The Ottawa Hospital Weight Management Clinic offers a course in lifestyle modification and uses 12 weeks of total meal replacement.

Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization.

Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause.

Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women.

Common Polymorphism That Protects From Cardiovascular Disease Increases Fibronectin Processing and Secretion.

Background: Fibronectin () is an essential regulator of homodynamic processes and tissue remodeling that have been proposed to contribute to atherosclerosis. Moreover, recent large-scale genome-wide association studies (GWAS) have linked common genetic variants within the gene to coronary artery disease risk.

Methods: Public databases were analyzed by 2-Sample Mendelian Randomization.

Epigenome-Wide Study Identified Methylation Sites Associated with the Risk of Obesity.

Here, we performed a genome-wide search for methylation sites that contribute to the risk of obesity. We integrated methylation quantitative trait locus (mQTL) data with BMI GWAS information through a SNP-based multiomics approach to identify genomic regions where mQTLs for a methylation site co-localize with obesity risk SNPs. We then tested whether the identified site contributed to BMI through Mendelian randomization.

A Common Polymorphism in the Locus Links miR1908 to Low-Density Lipoprotein Cholesterol Through BMP1.

OBJECTIVE: Leveraging microRNA-Seq data and the 1000 Genomes imputed genotypes, we identified rs174561 as a strong microRNA quantitative trait loci for circulating microRNA-1908-5p with higher miR-1908-5p and reduced LDL (lowdensity lipoprotein)-cholesterol, fasting glucose and A1c concentrations in carriers of the rs-174561-C allele. Here, we have investigated the molecular mechanism(s) linking miR-1908-5p to LDL-C concentrations. APPROACH AND RESULTS: Transfection experiments demonstrate that the presence of the C allele significantly increases miR- 1908-5p abundance relative to the T allele.

Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region.

Here we seek to identify molecular biomarkers that mediate the effect of risk factors on coronary artery disease (CAD). We perform a SNP-based multiomics data analysis to find biomarkers (probes) causally associated with the risk of CAD within known genomic loci for its risk factors. We identify 78 biomarkers, the majority (64%) of which are methylation probes.

Influence of synthetic wastewater on entrapped air on the isotactic and atactic polypropylene microplastic surfaces.

The municipal wastewater collection system is recognized as an initial point of interaction between microplastics (MPs) and the urban wastewater matrix. The raw wastewater contains a wide variety of organic and inorganic substances including chemicals and heavy metals. However, the fate of MPs in urban sewer systems is not yet well understood.

Publisher Correction: RIPK1 gene variants associate with obesity in humans and can be therapeutically silenced to reduce obesity in mice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

RIPK1 gene variants associate with obesity in humans and can be therapeutically silenced to reduce obesity in mice.

Obesity is a major public health burden worldwide and is characterized by chronic low-grade inflammation driven by the cooperation of the innate immune system and dysregulated metabolism in adipose tissue and other metabolic organs. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a central regulator of inflammatory cell function that coordinates inflammation, apoptosis and necroptosis in response to inflammatory stimuli. Here we show that genetic polymorphisms near the human RIPK1 locus associate with increased RIPK1 gene expression and obesity.

Multiomics Screening Identifies Molecular Biomarkers Causally Associated With the Risk of Coronary Artery Disease.

Background: In this study, we aimed to investigate functional mechanisms underlying coronary artery disease (CAD) loci and find molecular biomarkers for CAD.

Methods: We devised a multiomics data analysis approach based on Mendelian randomization and utilized it to search for molecular biomarkers causally associated with the risk of CAD within genomic regions known to be associated with CAD.

Results: Through our CAD-centered multiomics data analysis approach, we identified 33 molecular biomarkers (probes) that were causally associated with the risk of CAD.

Is a Long Non-coding RNA Locus That Regulates Expression.

Genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) most of them located in non-protein coding regions of the genome. One such locus is the CAD Associated Region between and (CARMA), a ∼18 kb haplotype that was recently shown to regulate vicinal protein coding genes. Here, we further investigate the region by examining a long non-coding RNA gene locus (RP11-326A19.

rs679482 Associates With Weight Loss Success in Response to an Intensively Supervised Outpatient Program.

Weight loss in response to energy restriction is highly variable, and identification of genetic contributors can provide insights into underlying biology. Leveraging 1000 Genomes imputed genotypes, we carried out genome-wide association study (GWAS) analysis in 551 unrelated obese subjects of European ancestry who participated in an intensively supervised weight loss program with replication of promising signals in an independent sample of 1,331 obese subjects who completed the program at a later date. By single nucleotide polymorphism-based and sib-pair analysis, we show that that weight loss is a heritable trait, with estimated heritability ( = 0.

Phenome-wide screening for traits causally associated with the risk of coronary artery disease.

Using two independent approaches, Mendelian randomization and Polygenic risk score in a sample of 6194 CAD cases and 4287 controls of European ancestry, we did a comprehensive phenome-wide search (PheWAS) for traits that causally associated with the risk of CAD. We found 46 risk factors that represented diverse categories including cardiovascular, CNS (central nervous system), diabetes, lipids, immune, anthropometry, and life style features; moreover, we noted numerous evidences of genetic correlations and causal associations between risk factors from different categories. Among the identified risk factors, CAD showed highest genetic relatedness with thrombotic conditions.

Regulation of MFGE8 by the intergenic coronary artery disease locus on 15q26.1.

Background And Aims: A recently identified locus for coronary artery disease (CAD) tagged by rs8042271 is in a region of tight linkage disequilibrium (LD) between 2 genes (MFGE8, ABHD2) previously linked to atherosclerosis. Here we have explored the regulatory framework of this region to identify its functional relationship to CAD.

Methods: The CAD Associated Region between MFGE8 and ABHD2 (CARMA) was investigated by bioinformatic approaches and transcriptional reporter assays to prioritize target genes and identify putative causal variants.

Partitioning the Pleiotropy Between Coronary Artery Disease and Body Mass Index Reveals the Importance of Low Frequency Variants and Central Nervous System-Specific Functional Elements.

Background: The objective of this study is to investigate the extent and nature of pleiotropy between coronary artery disease (CAD) and body mass index (BMI).

Methods: We examined the contribution of genome-wide single-nucleotide polymorphisms (minor allele frequency ≥0.01) to co-occurrence of CAD and BMI in a sample of genetically unrelated 8041 subjects (genetic resemblance ≤0.

Diet-resistant obesity is characterized by a distinct plasma proteomic signature and impaired muscle fiber metabolism.

Background/objectives: Inter-individual variability in weight loss during obesity treatment is complex and poorly understood. Here we use whole body and tissue approaches to investigate fuel oxidation characteristics in skeletal muscle fibers, cells and distinct circulating protein biomarkers before and after a high fat meal (HFM) challenge in those who lost the most (obese diet-sensitive; ODS) vs the least (obese diet-resistant; ODR) amount of weight in a highly controlled weight management program.

Subjects/methods: In 20 weight stable-matched ODS and ODR women who previously completed a standardized clinical weight loss program, we analyzed whole-body energetics and metabolic parameters in vastus lateralis biopsies and plasma samples that were obtained in the fasting state and 6 h after a defined HFM, equivalent to 35% of total daily energy requirements.

A Review of Surfactant Role in Soil Clogging Processes at Wastewater Exfiltration Locations in Sewers.

  Wastewater contains significant sources of pollutants and contaminants. often the failure of a pipe, inadequate sealing or corrupt pipe-connections cause the loss of raw sewage, which percolates into the nearby soil. As a consequence, a colmation layer in conjunction with soil clogging is developing, which regulates the exfiltration rate.

Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease.

Background: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.

Objectives: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.