TY - JOUR T1 - Phenotype-Specific Association of Single-Nucleotide Polymorphisms with Heart Failure and Preserved Ejection Fraction: a Genome-Wide Association Analysis of the Cardiovascular Health Study. JF - J Cardiovasc Transl Res Y1 - 2017 A1 - Kao, David P A1 - Stevens, Laura M A1 - Hinterberg, Michael A A1 - Görg, Carsten KW - Aged KW - Computational Biology KW - Databases, Genetic KW - European Continental Ancestry Group KW - Female KW - Gene Expression Profiling KW - Genetic Markers KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Heart Failure KW - Humans KW - Male KW - Oligonucleotide Array Sequence Analysis KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Predictive Value of Tests KW - Prognosis KW - Proteoglycans KW - Receptors, Transforming Growth Factor beta KW - Risk Assessment KW - Risk Factors KW - Stroke Volume KW - United States AB -

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.

VL - 10 IS - 3 ER -