Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Religious Diversity and Religious Vitality: New Measuring Strategies and Empirical Evidence

Quantitative studies of the conditions and consequences of religious diversity are based mostly on indices that measure the variety of religious membership in a particular region. However, this line of research has become stagnant, and the question of whether diversity affects religious vitality remains unanswered. This article attempts to shed new light on the discussion by measuring religious diversity differently and capturing religious vitality independently of membership figures. In particular, it contrasts the Herfindahl-Hirschman Index based on membership proportions with a second measure of diversity: an index of organizational diversity. Conversely, the dependent variable religious vitality is measured not by using rates of participation in religious organizations but via the Centrality of Religion Scale. Based on ecological and individual level data of forty-three local regions in Finland, Germany, and Slovenia and using multilevel analysis, our results suggest that religious diversity is related to religious vitality. However, the nature of this association differs across subgroups.