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Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Mosley, Jonathan D. Driest, Sara L. Van 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 J. Pacheco, Jennifer A. Peissig, Peggy L. Brilliant, Murray H. Linneman, James G. Denny, Joshua C. Roden, Dan M. |
| Copyright Year | 2016 |
| 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. |
| Starting Page | 521 |
| Ending Page | 530 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| DOI | 10.1161/CIRCGENETICS.116.001530 |
| PubMed reference number | 27780847 |
| Journal | Medline |
| Volume Number | 9 |
| Issue Number | 6 |
| Alternate Webpage(s) | http://circgenetics.ahajournals.org/content/circcvg/9/6/521.full.pdf?download=true |
| Alternate Webpage(s) | http://circgenetics.ahajournals.org/content/circcvg/early/2016/10/25/CIRCGENETICS.116.001530.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1161/CIRCGENETICS.116.001530 |
| Journal | Circulation. Cardiovascular genetics |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
