Metabolomic Profiling of Long-Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain.

Objective: To investigate the association between long-term weight change and blood metabolites.

Methods: Change in BMI over 8.6 ± 3.

Genome-wide association study identifies inversion in the locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis.

Objective: Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus.

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals.

Admission serum potassium concentration and long-term mortality in patients with acute myocardial infarction: results from the MONICA/KORA myocardial infarction registry.

Background: Conflicting with clinical practice guidelines, recent studies demonstrated that serum potassium concentrations (SPC) of ≥4.5 mEq/l were associated with increased mortality in patients with acute myocardial infarction (AMI). This study examined the association between SPC and long-term mortality following AMI in patients recruited from a population-based registry.

Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes.

Diabetes-associated metabolites may aid the identification of new risk variants for type 2 diabetes. Using targeted metabolomics within a subsample of the German EPIC-Potsdam study (n = 2500), we tested previously published SNPs for their association with diabetes-associated metabolites and conducted an additional exploratory analysis using data from the exome chip including replication within 2,692 individuals from the German KORA F4 study. We identified a total of 16 loci associated with diabetes-related metabolite traits, including one novel association between rs499974 (MOGAT2) and a diacyl-phosphatidylcholine ratio (PC aa C40:5/PC aa C38:5).

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10) or suggestively genome wide (p < 2.

Metabotyping and its application in targeted nutrition: an overview.

Metabolic diversity leads to differences in nutrient requirements and responses to diet and medication between individuals. Using the concept of metabotyping - that is, grouping metabolically similar individuals - tailored and more efficient recommendations may be achieved. The aim of this study was to review the current literature on metabotyping and to explore its potential for better targeted dietary intervention in subjects with and without metabolic diseases.

Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia.

Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME-ON) network.

Independent and opposite associations of serum levels of omentin-1 and adiponectin with increases of glycaemia and incident type 2 diabetes in an older population: KORA F4/FF4 study.

Objective: Cross-sectional studies found that higher levels of the novel adipokine omentin-1 were associated with higher adiponectin and lower levels of risk factors for type 2 diabetes, but its relevance for incident type 2 diabetes is currently not understood. Therefore this study investigated whether serum omentin-1 was associated with changes in glycaemia and incident type 2 diabetes independently of adiponectin.

Design And Methods: The study was based on participants aged 62-81 years from the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort.

Male sex and poverty predict abrupt health decline: Deficit accumulation patterns and trajectories in the KORA-Age cohort study.

Ageing individuals differ both in their deficit accumulation (DA) trajectories and resulting DA patterns (improvement, stability, gradual or abrupt decline). This heterogeneity is still incompletely understood. The objectives of this study were thus to identify determinants of DA trajectories and DA patterns in people aged 65 and older.

Attention, cognitive control and motivation in ADHD: Linking event-related brain potentials and DNA methylation patterns in boys at early school age.

In order to better understand the underpinnings of attention-deficit/hyperactivity disorder (ADHD), we targeted the relationship of attentional, cognitive control and motivational processes with DNA methylation patterns of 60 candidate genes in boys at early school age. Participants (6 to 8 years; N = 82) were selected from a German longitudinal cohort (FRANCES). ADHD-related behaviour was assessed via maternal ratings.

"In the mood for ageing": determinants of subjective well-being in older men and women of the population-based KORA-Age study.

Background: To investigate risk factors associated with low subjective well-being (SWB) in men and women (≥65 years) separately with a special focus on emotional distress.

Methods: A cross-sectional analysis was conducted among 3602 participants (50.6% women) aged 65-90 years (mean age 72.

Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4).

Blood pathway analyses reveal differences between prediabetic subjects with or without dyslipidaemia. The Cardiovascular Risk in Young Finns Study.

Background: Prediabetes often occurs together with dyslipidaemia, which is paradoxically treated with statins predisposing to type 2 diabetes mellitus. We examined peripheral blood pathway profiles in prediabetic subjects with (PR ) and without dyslipidaemia (PR ) and compared these to nonprediabetic controls without dyslipidaemia (C ).

Methods: The participants were from the Cardiovascular Risk in Young Finns Study, including 1240 subjects aged 34 to 49 years.

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci.

Ultra-sensitive troponin I is an independent predictor of incident coronary heart disease in the general population.

Troponins are sensitive markers of myocardial injury and predictive of cardiovascular events, but conventional assays fail to detect slightly elevated troponins in a considerable proportion of the general population. Using a novel ultrasensitive assay, we explored the relationship of troponin levels with the incidence of coronary heart disease (CHD) in a case-cohort sample (mean age 52.5 ± 0.

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.

To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci ( < 5 × 10), including variants near the , , and genes.

Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model.

Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32-72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation.

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects.

24 h-accelerometry in epidemiological studies: automated detection of non-wear time in comparison to diary information.

Estimation of physical activity using 24 h-accelerometry requires detection of accelerometer non-wear time (NWT). It is common practice to define NWT as periods >60 minutes of consecutive zero-accelerations, but this algorithm was originally developed for waking hours only and its applicability to 24 h-accelerometry is unclear. We investigated sensitivity and specificity of different algorithms to detect NWT in 24 h-accelerometry compared to diary in 47 ActivE and 559 KORA participants.

Pancreatic fat content by magnetic resonance imaging in subjects with prediabetes, diabetes, and controls from a general population without cardiovascular disease.

Background/objective: Despite the relevance of pancreatic fat content in the development of metabolic diseases, its association with impaired glucose metabolism, diabetes, and other adipose tissue compartments remains unclear. Thus, we determined differences in pancreatic fat content by magnetic resonance imaging (MRI) between subjects with prediabetes, diabetes, and normal controls in a cohort from the general population.

Methods: Subjects without history of cardiovascular disease with established diabetes or prediabetes as well as normal controls were included and underwent whole-body MRI on a 3T scanner.

Plasma and Serum Metabolite Association Networks: Comparability within and between Studies Using NMR and MS Profiling.

Blood is one of the most used biofluids in metabolomics studies, and the serum and plasma fractions are routinely used as a proxy for blood itself. Here we investigated the association networks of an array of 29 metabolites identified and quantified via NMR in the plasma and serum samples of two cohorts of ∼1000 healthy blood donors each. A second study of 377 individuals was used to extract plasma and serum samples from the same individual on which a set of 122 metabolites were detected and quantified using FIA-MS/MS.

A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.

High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n = 13,781).

Association between dietary inflammatory index, and cause-specific mortality in the MONICA/KORA Augsburg Cohort Study.

Background: Chronic diseases such as cancer and cardiovascular diseases (CVDs) are well-established causes of disability and premature death. Dietary components have been implicated in the etiology of these chronic diseases.

Methods: We examined the ability of the Dietary Inflammatory Index (DIITM) to predict all-cause, coronary heart disease (CHD), CVD and cancer mortality and incident CHD in the MONICA-KORA Cohort Studies.