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 quantitate 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 Atherosclerosis Risk in Communities (ARIC) study (n=7,716 European ancestry subjects) and clinical diagnoses from an electronic health record (EHR) data set (n=19,093). All subjects had genome-wide SNP 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’s correlation [r]=0.62), indicating that the two IHD phenotypes had differing risk profiles. For comparison, this correlation was 0.80 when comparing EHR and ARIC type 2 diabetes (T2D) phenotypes. The EHR IHD phenotype was most strongly correlated with ARIC metabolic phenotypes including total-to-HDL cholesterol ratio (rG=−0.44, p=0.005), HDL (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 T2D, 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.