Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data

Jonathan D. Mosley, Sara L. Van Driest, Quinn S. Wells, Christian M. Shaffer, Todd L. Edwards, Lisa Bastarache, Catherine A. McCarty, Will Thompson, Christopher G. Chute, Gail P. Jarvik, David R. Crosslin, Eric B. Larson, Iftikhar Jan Kullo, Jennifer A. Pacheco, Peggy L. Peissig, Murray H. Brilliant, James G. Linneman, Josh C. Denny, Dan M. Roden

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background-Continued reductions in morbidity and mortality attributable to ischemic heart disease (IHD) require an understanding of the changing epidemiology of this disease. We hypothesized that we could use genetic correlations, which quantify the shared genetic architectures of phenotype pairs and extant risk factors from a historical prospective study to define the risk profile of a contemporary IHD phenotype. Methods and Results-We used 37 phenotypes measured in the ARIC study (Atherosclerosis Risk in Communities; n=7716, European ancestry subjects) and clinical diagnoses from an electronic health record (EHR) data set (n=19 093). All subjects had genome-wide single-nucleotide polymorphism genotyping. We measured pairwise genetic correlations (rG) between the ARIC and EHR phenotypes using linear mixed models. The genetic correlation estimates between the ARIC risk factors and the EHR IHD were modestly linearly correlated with hazards ratio estimates for incident IHD in ARIC (Pearson correlation [r]=0.62), indicating that the 2 IHD phenotypes had differing risk profiles. For comparison, this correlation was 0.80 when comparing EHR and ARIC type 2 diabetes mellitus phenotypes. The EHR IHD phenotype was most strongly correlated with ARIC metabolic phenotypes, including total:high-density lipoprotein cholesterol ratio (rG=-0.44, P=0.005), high-density lipoprotein (rG=-0.48, P=0.005), systolic blood pressure (rG=0.44, P=0.02), and triglycerides (rG=0.38, P=0.02). EHR phenotypes related to type 2 diabetes mellitus, atherosclerotic, and hypertensive diseases were also genetically correlated with these ARIC risk factors. Conclusions-The EHR IHD risk profile differed from ARIC and indicates that treatment and prevention efforts in this population should target hypertensive and metabolic disease.

Original languageEnglish (US)
Pages (from-to)521-530
Number of pages10
JournalCirculation: Cardiovascular Genetics
Volume9
Issue number6
DOIs
StatePublished - Dec 1 2016

Fingerprint

Myocardial Ischemia
Electronic Health Records
Phenotype
Type 2 Diabetes Mellitus
Blood Pressure
Health Services Needs and Demand
Metabolic Diseases
HDL Lipoproteins
HDL Cholesterol
Single Nucleotide Polymorphism
Linear Models
Atherosclerosis
Epidemiology
Triglycerides
Genome
Prospective Studies
Morbidity
Mortality

Keywords

  • atherosclerosis
  • blood pressure
  • coronary artery disease
  • risk factors
  • triglycerides

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

Mosley, J. D., Van Driest, S. L., Wells, Q. S., Shaffer, C. M., Edwards, T. L., Bastarache, L., ... Roden, D. M. (2016). Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data. Circulation: Cardiovascular Genetics, 9(6), 521-530. https://doi.org/10.1161/CIRCGENETICS.116.001530

Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data. / Mosley, Jonathan D.; Van Driest, Sara L.; Wells, Quinn S.; Shaffer, Christian M.; Edwards, Todd L.; Bastarache, Lisa; McCarty, Catherine A.; Thompson, Will; Chute, Christopher G.; Jarvik, Gail P.; Crosslin, David R.; Larson, Eric B.; Kullo, Iftikhar Jan; Pacheco, Jennifer A.; Peissig, Peggy L.; Brilliant, Murray H.; Linneman, James G.; Denny, Josh C.; Roden, Dan M.

In: Circulation: Cardiovascular Genetics, Vol. 9, No. 6, 01.12.2016, p. 521-530.

Research output: Contribution to journalArticle

Mosley, JD, Van Driest, SL, Wells, QS, Shaffer, CM, Edwards, TL, Bastarache, L, McCarty, CA, Thompson, W, Chute, CG, Jarvik, GP, Crosslin, DR, Larson, EB, Kullo, IJ, Pacheco, JA, Peissig, PL, Brilliant, MH, Linneman, JG, Denny, JC & Roden, DM 2016, 'Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data', Circulation: Cardiovascular Genetics, vol. 9, no. 6, pp. 521-530. https://doi.org/10.1161/CIRCGENETICS.116.001530
Mosley, Jonathan D. ; Van Driest, Sara L. ; Wells, Quinn S. ; Shaffer, Christian M. ; Edwards, Todd L. ; Bastarache, Lisa ; McCarty, Catherine A. ; Thompson, Will ; Chute, Christopher G. ; Jarvik, Gail P. ; Crosslin, David R. ; Larson, Eric B. ; Kullo, Iftikhar Jan ; Pacheco, Jennifer A. ; Peissig, Peggy L. ; Brilliant, Murray H. ; Linneman, James G. ; Denny, Josh C. ; Roden, Dan M. / Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data. In: Circulation: Cardiovascular Genetics. 2016 ; Vol. 9, No. 6. pp. 521-530.
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