Approved research

Genetic dissection of the relationships of myocardial diseases and their risk factors

Lay summary

GWAS has been successful in identifying common genetic variants contributing to polygenic inheritance of common, etiologically complex diseases. However, for the major myocardial diseases heart failure and atrial fibrillation, leading causes of hospitalization in western countries, cohorts have been lacking and progress has been limited. Analysis of these traits are further complicated by the interplay of the two diseases and their risk factors. We plan to perform GWAS for these related traits and their risk factors in the UK Biobank, as well as mortality and stroke outcomes, and sensitivity analyses across etiological subgroups of HF/AF. We believe that this research proposal is consistent with UK Biobank's purposes to improve understanding of the causes of common diseases and improve public health. The proposed project will leverage this unique resource to provide novel pathophysiological insights into the etiology and pathophysiology of myocardial disease, a major cause of disease burden globally. We anticipate that our findings will facilitate improvements in therapy for these diseases. We will investigate the association of genetic variation across the entire human genome with two major myocardial diseases, heart failure (HF) and atrial fibrillation, and with prognosis and co-occurence of these diseases. Outcomes will be captured based on ICD codes for hospital inpatients and outpatients. To account for the heterogeneity of HF, we will perform additional analyses specific to subgroups of HF and AF. Associations meeting a level of statistical significance for the entire genome (p-value < 5x10-8) will be considered significant. We plan to include the full cohort to maximize the ability to examine the interplay of risk factors on HF/AF risk.