Dan Roden
Faculty Member
Last active: 3/24/2020

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

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
Circ Cardiovasc Genet. 2016 9 (6): 521-530

PMID: 27780847 · PMCID: PMC5177499 · DOI:10.1161/CIRCGENETICS.116.001530

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.

© 2016 American Heart Association, Inc.

MeSH Terms (31)

Aged Aged, 80 and over Atherosclerosis Blood Pressure Case-Control Studies Chi-Square Distribution Cross-Sectional Studies Diabetes Mellitus, Type 2 Electronic Health Records Female Genetic Markers Genetic Predisposition to Disease Genome-Wide Association Study Humans Hypertension Incidence Linear Models Lipids Male Middle Aged Molecular Epidemiology Myocardial Ischemia Phenotype Polymorphism, Single Nucleotide Prevalence Prognosis Proportional Hazards Models Risk Assessment Risk Factors Time Factors United States

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