Whole blood DNA methylation signatures of diet are associated with cardiovascular disease risk factors and all-cause mortality

Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni correctedP<1.6x10(-3)). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7x10(-15)). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MRP<4.5x10(-4)). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR,P=1.5x10(-14)).and hypermethylation of cg02079413 (SNORA54;NAP1L4) was associated with body mass index (corrected MR,P=1x10(-6)). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Peer reviewe

Meta-analyses identify DNA methylation associated with kidney function and damage

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.</p

Meta-analyses identify DNA methylation associated with kidney function and damage

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.Many genetic loci have been identified to be associated with kidney disease, but the molecular mechanisms are not well understood. Here, the authors perform epigenome-wide association studies on kidney function measures to identify epigenetic marks and pathways involved in kidney function.</p

Applicability of a SPME method for the Rapid Determination of VOCs

A fast method for monitoring volatile organic compounds in water and air is described whereby the VOCs are adsorbed on a SPME and then desorbed directly in a flame ionization detector (FID) or a photoionization detector (PID). The signal obtained provides a global measure of the VOCs present in water or air. In most cases, such as accidental pollution by hydrocarbons, wastewater from industry or control of the absence of solvent in air, this information is very relevant. The analysis can be handled by a non-professional with a throughput of 10 samples/h. Low levels of about 10?g organic volatile compounds per liter of water can be measured

Monitoring of the Drying Process by Direct Solid-Phase Microextraction: FH – HES

SPME is known as a rapid and convenient method for analyzing air-borne organic compounds in closed systems ('headspace SPME'). In this investigation we have applied this technique to the monitoring of the drying process of chemicals containing small amounts of organic solvents under specific conditions. Interesting results were found and some of them are presented and discussed in this paper

Nucleotide and Nucleotide Sugar Analysis in Cell Extracts by Capillary Electrophoresis: FH-HES Universities of Applied Sciences

In biotechnological processes the intracellular level of nucleotides and nucleotide sugars have a direct impact on the post-translational modification (glycosylation) of the therapeutic protein products and on the exopolysaccharide pattern of the cells. Thus, they are precursors and also key components in the production of glycoproteins and glycolipids. All four nucleotides (at different phosphorylation stages) and their natural sugar derivatives coexist in biological samples. Their relative ratios depend on the actual conditions under which the cells are grown. Therefore, their simultaneous determination at different time points and different cell culture conditions in biotechnological samples is of interest in order to develop the optimal cell culture process. In our study capillary electrophoresis (CE) combined with UV detection @ 260 nm was selected for the separation and quantification of the complex nucleotide mixture of the structurally very similar nucleotides and nucleotide sugars in cell extracts. The high separation efficiency of CE as well as its insensitivity to the complex cell matrix makes this method superior to commonly used HPLC methods. In our study eleven nucleotides and six nucleotide sugars were analyzed. A robust and reproducible analysis system was developed. As background electrolyte borate (40 mM, pH 9.5) was used containing 1% PEG (MW 35'000 Da) which enhanced resolution. In order to obtain high reproducibility in terms of migration time, mandatory for the unambiguous identification of the single compounds in the complex cell extract mixtures, dynamic coating was also employed. The method was tested for CHO cell extracts where three sugar nucleotides and seven nucleotides were identified and quantified using GDP-Glc as internal standard

Nucleotide and nucleotide sugar analysis in cell extracts by capillary electrophoresis

In biotechnological processes the intracellular level of nucleotides and nucleotide sugars have a direct impact on the post-translational modification (glycosylation) of the therapeutic protein products and on the exopolysaccharide pattern of the cells. Thus, they are precursors and also key components in the production of glycoproteins and glycolipids. All four nucleotides (at different phosphorylation stages) and their natural sugar derivatives coexist in biological samples. Their relative ratios depend on the actual conditions under which the cells are grown. Therefore, their simultaneous determination at different time points and different cell culture conditions in biotechnological samples is of interest in order to develop the optimal cell culture process. In our study capillary electrophoresis (CE) combined with UV detection @ 260 nm was selected for the separation and quantification of the complex nucleotide mixture of the structurally very similar nucleotides and nucleotide sugars in cell extracts. The high separation efficiency of CE as well as its insensitivity to the complex cell matrix makes this method superior to commonly used HPLC methods. In our study eleven nucleotides and six nucleotide sugars were analyzed. A robust and reproducible analysis system was developed. As background electrolyte borate (40 mM, pH 9.5) was used containing 1% PEG (MW 35'000 Da) which enhanced resolution. In order to obtain high reproducibility in terms of migration time, mandatory for the unambiguous identification of the single compounds in the complex cell extract mixtures, dynamic coating was also employed. The method was tested for CHO cell extracts where three sugar nucleotides and seven nucleotides were identified and quantified using GDP-Glc as internal standard

Enzymatic synthesis of 6- and 6′-O-linoleyl-α-D-maltose ::from solvent-free to binary ionic liquid reaction media

The eco-efficient lipase catalyzed synthesis of sugar fatty acid ester surfactants from renewable commodities is a stimulating challenge in biotransformation. The biocatalytic investigations went from solvent-free and minimal ionic liquid use to bulk organic solvents, and binary solvents thereof. Disaccharide maltose was acylated with linoleic acid (C18:2) on the primary O-6,6′ hydroxyl functions. The ionic liquid [emim][MeSO3] and the potentially renewable acetone enabled best conversions. Binary solvents like acetone/DMF and [emim][MeSO3]/[bmpyr][PF6] tended to double conversions. The lipase selection is also crucial and the enzymes Pseudomonas cepacia and immobilized Candida antarctica allowed highest yields in a screening with 10 different lipases. Also other non-solvent parameters such as reaction time and molecular sieve content improved maltose transformation further up to 82%. Analysis by HPLC, ESI-MS, and NMR indicated the formation of mono-6 or 6′-O-linoleyl-α-d-maltose as a mixture of two regioisomers in a 1.4:1 ratio. From an applied point of view, the best solvent is acetone. Unlike ionic liquids and binary mixtures, it is easily removable from reaction mixtures. Moreover, acetone is to some degree a green solvent as it can be produced directly from renewable feedstock