: Return 2685

Notes

We performed a population-based genetic association study of all-cause heart failure that yielded multiple genetic signals for known heart failure risk factors, such as coronary artery disease and atrial fibrillation. Refining the heart failure phenotype to a non-ischemic cardiomyopathy subset enhanced the detection of genetic loci associated with dilated cardiomyopathy, which appear to operate independent of traditional heart failure risk factors. Genetic variants associated with nonischemic cardiomyopathy were also associated with subclinical traits of left ventricular dysfunction.

Application 17488

Understanding the Genetic Basis of Cardiac Arrhythmias

Cardiac arrhythmias are leading causes of morbidity and sudden death, however the pathophysiologic basis of arrhythmias largely remains unclear. In recent years, heritability of arrhythmias has been described suggesting a genetic basis. We specifically intend to identify the genetic causes of cardiac arrhythmias, assess the causal relations between cardiac arrhythmias and long-term morbidity, estimate the long-term risks of genetic predisposition to cardiac arrhythmias, and determine the relations between cardiac arrhythmias and other cardiovascular traits including cardiac conduction, cardiac structural features, and myocardial related biomarkers. Cardiac arrhythmias are a common source of morbidity, yet the mechanisms are poorly understood. Our proposal is designed to address the genetic underpinnings of cardiac arrhythmias, and assess their relations with morbidity. Our proposal has the potential to provide novel insights into the pathophysiological and biological mechanisms of cardiac arrhythmias. We believe that our findings may yield novel preventative, diagnostic, and therapeutic insights. We submit that our proposal is consistent with the UK Biobank's goal of improving the understanding of common diseases and improving public health. We will examine the genetic underpinnings of common cardiac arrhythmias, including tachyarrhythmias (disorders involving fast heart rates, such as supraventricular tachycardias), and bradyarrhythmias (disorders involving slow heart rates, such as those necessitating pacemaker implantation). Phenotypes will be ascertained on the basis of diagnostic codes (ICD), procedure codes and operations, and self-report. The research will involve both common and rare variant genetic association testing across the genome with cardiac arrhythmia phenotypes. The results of analyses will be meta-analyzed with other independent analyses to enhance power. We will use contemporary statistical approaches and significance thresholds for determining significance. We anticipate using the full cohort for this proposal.

Lead investigator:	Dr Steven Lubitz
Lead institution:	Broad Institute

4 related Returns

Return ID	App ID	Description	Archive Date
2686	17488	Association Between Titin Loss-of-Function Variants and Early-Onset Atrial Fibrillation	30 Oct 2020
2687	17488	Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults	30 Oct 2020
2689	17488	Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation	30 Oct 2020
2688	17488	Multi-Ethnic Genome-wide Association Study for Atrial Fibrillation	30 Oct 2020

1 Publication

Pub ID	Title	Author(s)	Year	Journal
2686	Phenotypic Refinement of Heart Failure in a National Biobank Facilitates Genetic Discovery	Krishna G. Aragam (+22)	2018	Circulation

Application:	17488, Understanding the Genetic Basis of Cardiac Arrhythmias
Title:	Phenotypic Refinement of Heart Failure in a National Biobank Facilitates Genetic Discovery
Size:	524295 B
Archived:	30 Oct 2020
Stability:	Complete
Personal:	No individual-level data