title: Phenotype-Specific Association of Single-Nucleotide Polymorphisms with Heart Failure and Preserved Ejection Fraction: a Genome-Wide Association Analysis of the Cardiovascular Health Study.
abstract: 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.
authors.affiliation: University of Colorado School of Medicine, 12700 E 19th Ave Campus Box B-139, Aurora, CO, 80045, USA. David.Kao@ucdenver.edu.
authors.forename: David P
authors.initials: DP
authors.lastname: Kao
authors.affiliation: University of Colorado School of Medicine, 12700 E 19th Ave Campus Box B-139, Aurora, CO, 80045, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Stevens
authors.affiliation: University of Colorado School of Medicine, 12700 E 19th Ave Campus Box B-139, Aurora, CO, 80045, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hinterberg
authors.affiliation: University of Colorado School of Medicine, 12700 E 19th Ave Campus Box B-139, Aurora, CO, 80045, USA.
authors.forename: Carsten
authors.initials: C
authors.lastname: Görg
mesh_terms: D000368:Aged; D019295:Computational Biology; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006333:Heart Failure / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D011509:Proteoglycans / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D005819:Genetic Markers; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan
keywords: Atrial fibrillation; Chronic kidney disease; Chronic obstructive pulmonary disease; Comorbidities; Coronary artery disease; Genome-wide association study; Heart failure phenotype; Heart failure with preserved ejection fraction; Hypertension