Journal
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
Volume 10, Issue 3, Pages 285-294Publisher
SPRINGER
DOI: 10.1007/s12265-017-9729-1
Keywords
Heart failure with preserved ejection fraction; Genome-wide association study; Heart failure phenotype; Comorbidities; Atrial fibrillation; Chronic obstructive pulmonary disease; Coronary artery disease; Hypertension; Chronic kidney disease
Funding
- American Heart Association Cardiovascular Phenome-Genome Study Award [15CVGPSD27090024]
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Little is known about genetics of heart failure with preserved ejection fraction (HFpEF) in part because of the many comorbidities in this population. To identify single-nucleotide polymorphisms (SNPs) associated with HFpEF, we analyzed phenotypic and genotypic data from the Cardiovascular Health Study, which profiled patients using a 50,000 SNP array. Results were explored using novel SNP-and gene-centric tools. We performed analyses to determine whether some SNPs were relevant only in certain phenotypes. Among 3804 patients, 7 clinical factors and 9 SNPs were significantly associated with HFpEF; the most notable of which was rs6996224, a SNP associated with transforming growth factor-beta receptor 3. Most SNPs were associated with HFpEF only in the absence of a clinical predictor. Significant SNPs represented genes involved in myocyte proliferation, transforming growth factor-beta/erbB signaling, and extracellular matrix formation. These findings suggest that genetic factors may be more important in some phenotypes than others.
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