Phenotype-Specific Association of Single-Nucleotide Polymorphisms with Heart Failure and Preserved Ejection Fraction: a Genome-Wide Association Analysis of the Cardiovascular Health Study

被引:14
作者
Kao, David P. [1 ]
Stevens, Laura M. [1 ]
Hinterberg, Michael A. [1 ]
Gorg, Carsten [1 ]
机构
[1] Univ Colorado, Sch Med, 12700 E 19th Ave Campus Box B-139, Aurora, CO 80045 USA
关键词
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; EXTRACELLULAR-MATRIX; FIBROSIS; PATHOPHYSIOLOGY; COMORBIDITIES; HYPERTROPHY; STRATEGIES; KNOWLEDGE; DATABASE; MODELS; PLINK;
D O I
10.1007/s12265-017-9729-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:285 / 294
页数:10
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