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

Diet in subjects with irritable bowel syndrome: A cross-sectional study in the general population

<p>Abstract</p> <p>Background</p> <p>Patients with irritable bowel syndrome (IBS) often relate symptoms to the intake of certain foods. This study assesses differences in diet in subjects with and without IBS.</p> <p>Methods</p> <p>The cross-sectional, population-based study was conducted in Norway in 2001. Out of 11078 invited subjects, 4621 completed a survey about abdominal complaints and intake of common food items. IBS and IBS subgroups were classified according to Rome II criteria.</p> <p>Results</p> <p>IBS was diagnosed in 388 subjects (8.4%) and, of these, 26.5% had constipation-predominant IBS (C-IBS), 44.8% alternating IBS (A-IBS), and 28.6% diarrhoea-predominant IBS (D-IBS). Low intake of dairy products (portions/day) (Odds Ratio 0.85 [CI 0.78 to 0.93], p <it>=</it> 0.001) and high intake of water (100 ml/day) (1.08 [1.02 to 1.15], p <it>=</it> 0.002), tea (1.05 [1.01 to 1.10], p <it>=</it> 0.019) and carbonated beverages (1.07 [1.01 to 1.14], p <it>=</it> 0.023) were associated with IBS. A lower intake of dairy products and a higher intake of alcohol and carbonated beverages were associated with D-IBS and a higher intake of water and tea was associated with A-IBS. In subjects with IBS the severity of symptoms was associated with a higher intake of vegetables and potatoes in subjects with C-IBS, with a higher intake of vegetables in subjects with A-IBS, and with a higher intake of fruits and berries, carbonated beverages and alcohol in subjects with D-IBS.</p> <p>Conclusions</p> <p>In this study, the diet differed in subjects with and without IBS and between IBS subgroups and was associated with the severity of symptoms.</p