Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Proceedings of International Science Foundation Brainpower Forum, 1958

Held August 6-8, 1958, U.S. Naval Postgraduate School, Monterey, California[A]t the invitation of Rear Admiral Earl E. Stone, USN, then Superintendent of the U. S. Naval Postgraduate Scrnol, approximately sixty leaders in industry, government, and education met in Monterey, California, October 24-25, 1956, for the first conference of the !SF Brainpower Forum. This conference served to highlight the fact that we had not effectively utilized all sources of scientific manpower which were presently available. At the recommendations of the Forum partici- pants, the International Science Foundation initiated a continuing pro- gram in the area of scientific manpower and suggested that several of its members set up projects which would provide answers to some of the problems considered at the 1956 conference. As a matter of first priority, it was decided to give consideration to the gains that might be realized by giving recognition to and seeking better utilization of retired or senior professional manpower. The 1958 conference was held to give Forum participants an opportunity to report on projects in the area of senior scientific manpower that were conducted as a result of suggestions made at the 1956 conference. Among the NPS participants: Roy S. Glasgow, Dean; Captain H. M. Heming, USN, Director, Engineering School; Frank E. LaCauza, Academic Chairman, General Line and Naval Science School; Captain Paul Foley, Jr., USN, Chief of Staff; Dr. Austin R. Frey, Chairman, Department of Physics; Mitchell L. Cotton, Assistant Professor of Engineering ElectronicsThe following members of the International Science Foundation have served as the sponsors of this 1958 Conference of the Brainpower Forum: Stauffer Chemical Company, General Electric Company, U. S. Army Ordnance Missile Command. U. S. Naval Postgraduate School, Cooperative Research Institute, The Firestone Tire & Rubber Company, Federal Pacific Electric Company, Rheem Manufacturing Company, Northrop Aircraft, Inc., Standard Oil Company of California, Varian Associates, Ford Motor Company, Tidewater Oil Compan