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

Advancing the Landscape of Multimessenger Science in the Next Decade

Engel K, Lewis T, Muzio MS, et al. Advancing the Landscape of Multimessenger Science in the Next Decade. arXiv:2203.10074. 2022.The last decade has brought about a profound transformation in multimessenger science. Ten years ago, facilities had been built or were under construction that would eventually discover the nature of objects in our universe could be detected through multiple messengers. Nonetheless, multimessenger science was hardly more than a dream. The rewards for our foresight were finally realized through IceCube's discovery of the diffuse astrophysical neutrino flux, the first observation of gravitational waves by LIGO, and the first joint detections in gravitational waves and photons and in neutrinos and photons. Today we live in the dawn of the multimessenger era. The successes of the multimessenger campaigns of the last decade have pushed multimessenger science to the forefront of priority science areas in both the particle physics and the astrophysics communities. Multimessenger science provides new methods of testing fundamental theories about the nature of matter and energy, particularly in conditions that are not reproducible on Earth. This white paper will present the science and facilities that will provide opportunities for the particle physics community renew its commitment and maintain its leadership in multimessenger science