Search results for "MIZA"
showing 10 items of 3318 documents
Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases
2021
Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). However, in the last decades, genome-wide association studies (GWAS) have also suggested a polygenic inheritance o…
MicroRNAs and Drinking : Association between the Pre-miR-27a rs895819 Polymorphism and Alcohol Consumption in a Mediterranean Population
2016
Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consumption at the population level. Our aim was to investigate the association between a functional polymorphism in the pre-miR-27a (rs895819 A>G) gene and alcohol consumption in an elderly population. We undertook a cross-sectional study of PREvención con DIeta MEDiterránea (PREDIMED)-Valencia participants (n = 1007, including men and women aged 67 7 years) and measured their alcohol consumption (to…
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
2018
International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 1…
Does education protect against depression? Evidence from the Young Finns Study using Mendelian randomization
2018
Using participants (N = 1733) drawn from the nationally representative longitudinal Young Finns Study (YFS) we estimate the effect of education on depressive symptoms. In 2007, when the participants were between 30 and 45 years old, they reported their depressive symptoms using a revised version of Beck's Depression Inventory. Education was measured using register information on the highest completed level of education in 2007, which was converted to years of education. To identify a causal relationship between education and depressive symptoms we use an instrumental variables approach (Mendelian randomization, MR) with a genetic risk score as an instrument for years of education. The genet…
Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score: An Analysis of Hokusai-VTE.
2019
Background Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved. Aims We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial. Patients and Methods A total of 3,874 patients were included in the primary analysis (day 31–180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding. Results The rates of recurrent VTE and bleeding events we…
Search for a Minimal Set of Parameters by Assessing the Total Optimization Potential for a Dynamic Model of a Biochemical Network.
2017
Selecting an efficient small set of adjustable parameters to improve metabolic features of an organism is important for a reduction of implementation costs and risks of unpredicted side effects. In practice, to avoid the analysis of a huge combinatorial space for the possible sets of adjustable parameters, experience-, and intuition-based subsets of parameters are often chosen, possibly leaving some interesting counter-intuitive combinations of parameters unrevealed. The combinatorial scan of possible adjustable parameter combinations at the model optimization level is possible; however, the number of analyzed combinations is still limited. The total optimization potential (TOP) approach is…
A Dirichlet Autoregressive Model for the Analysis of Microbiota Time-Series Data
2021
Growing interest in understanding microbiota dynamics has motivated the development of different strategies to model microbiota time series data. However, all of them must tackle the fact that the available data are high-dimensional, posing strong statistical and computational challenges. In order to address this challenge, we propose a Dirichlet autoregressive model with time-varying parameters, which can be directly adapted to explain the effect of groups of taxa, thus reducing the number of parameters estimated by maximum likelihood. A strategy has been implemented which speeds up this estimation. The usefulness of the proposed model is illustrated by application to a case study.
Metabolic complementation in bacterial communities: Necessary conditions and optimality
2016
Bacterial communities may display metabolic complementation, in which different members of the association partially contribute to the same biosynthetic pathway. In this way, the end product of the pathway is synthesized by the community as a whole. However, the emergence and the benefits of such complementation are poorly understood. Herein, we present a simple model to analyze the metabolic interactions among bacteria, including the host in the case of endosymbiotic bacteria. The model considers two cell populations, with both cell types encoding for the same linear biosynthetic pathway. We have found that, for metabolic complementation to emerge as an optimal strategy, both product inhib…
Genetically elevated gamma-glutamyltransferase and Alzheimer's disease
2018
Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer's disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer's Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associ…
Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
2017
AbstractThe association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL includin…