Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, transethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N = 78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P < 5 x 10(-8)), we found suggestive evidence (P < 5 x 10(-6)) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. </p

Alpha-cyclodextrin as a new functional ingredient in low-fat chicken frankfurter

The current consumer preference for healthier meat products is associated with less additives in manufacturing (so-called ‘clean-label’) or the addition of non-meat ingredients with functional properties, recognised as improving specific technological properties in meat products. This study evaluated the effect of the addition of alpha-cyclodextrin and wheat fibre to low-fat chicken frankfurters containing 35% mechanically deboned chicken meat on the technological and sensorial properties during refrigerated storage. The results showed that the addition of dietary fibres (alpha-cyclodextrin and wheat fibre) in low-fat chicken frankfurters improved emulsion stability, hardness, chewiness and reduced cohesiveness. Alpha-cyclodextrin helped the retention of fat globules in the microstructure and affected colour in the sensorial evaluation. The use of alpha-cyclodextrin, in combination with wheat fibre, as a new ingredient to substitute fat in emulsified meat products containing mechanically deboned chicken, improved emulsion stability and texture. Alpha-cyclodextrin and wheat fibre were effective in contributing to fat reduction without affecting the sensory properties of the product606716723CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQNão te

Can dietary fiber improve the technological characteristics and sensory acceptance of low-fat Italian type salami?

To meet the needs of new consumers, meat researchers need to develop healthier products. Dietary fibers can be added for structural purposes, to present functional characteristics or to change the composition of the final product. In this study, mixture design was used to investigate the effects of partial substitution of pork fat by inulin, fructooligosaccharides and alpha-cyclodextrin on the technological and sensory quality characteristics of low-fat Italian type salami. The partial substitution of fat using dietary fibers shows no effect on weight loss, Aw and pH during ripening time. However, the addition of up to 2% alpha-cyclodextrin increased lightness and reduced redness and yellowness. Up to 2% of inulin or fructooligosaccharides added improved the sensory acceptance, texture parameters and redness. Healthier low-fat Italian type salami can be produced using inulin or fructooligosaccharides as fat substitute for pork fat and still obtain good technological and sensorial results571003101