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.

Saving the Australian War Effort in 1916? The Significance and Impact of Global Climatic Conditions and Pests on William Morris Hughes’ Negotiations with the British Government

Taking up the thesis of Dipesh Chakrabarty (2009) that human history (including cultural history) on the one hand and natural history on the other must be brought into conversation more than has been done so in the past, this presentation will focus more closely on the significance and the impact of global climatic conditions and pests on the negotiations that Australian Prime Minister William Morris Hughes carried on with the British government between March and November 1916. Whereas Australia had been able to sell most of its produce in 1914 and 1915 the situation looked more serious in 1916, not least due to the growing shortage in shipping. It was therefore imperative for the Australian government to find a way to solve this problem, not least because it wanted to keep up its own war effort at the pace it had been going so far. In this context intentions to make or press ahead with a contribution to a war perceived to be more total those of the past interacted with natural phenomena such as the declining harvest in many parts of the world in 1916 as a consequence of climatic conditions as well as pests in many parts of the world.