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.

Meta-analysis identifies seven susceptibility loci involved in the atopic march.

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

Geheime Netzwerke im Militär 1700-1945

Die Armee ist ein zentraler Machtfaktor im Staat, militärische Informationen sind grundsätzlich gesetzlich geschützt. Das Militär bildet zudem ein soziales System mit eigenen Normen, Ritualen und Symbolen. Die hierarchische Struktur und das starke Berufsethos prägen das Militär bis heute. Innerhalb dieses Rahmens bildeten sich immer wieder geheime Netzwerke von Militärangehörigen mit abweichenden Verhaltenskodizes. Sie erregten häufig den Verdacht, gegen das eigene Militärsystem oder den Staat gerichtet zu sein. Die Autorinnen und Autoren des Bandes erkunden die Wechselwirkungen zwischen Geheimbundorganisationen, Geheimnisträgern, Verschwörern und dem Militär – von Freimaurern und Illuminaten bis zum Stauffenberg-Kreis. Das Buch enthält Beiträge in deutscher und englischer Sprache