| Autor: |
Huang, Rose D, Nguyen, Xuan-Mai T, Djousse, Luc, Cho, Kelly, Gaziano, J. Michael, Wilson, Peter, Huffman, Jennifer E, O?Donnell, Christopher J |
| Zdroj: |
Circulation (Ovid); November 2019, Vol. 140 Issue: Supplement 1 pA14082-A14082, 1p |
| Abstrakt: |
Introduction:The American Heart Association introduced the concept of ideal cardiovascular (CV) health defined by optimal levels of behavioral and clinical factors that are each associated with lower risk of CV disease. A recent genome-wide association study (GWAS) of ideal CV health revealed a protective variant in the apolipoprotein E (APOE) gene in ~12,000 participants of European descent. We sought to examine genetic determinants of ideal CV health in a large, multi-ethnic biobank cohort of participants in the Million Veteran Program (MVP).Hypothesis:Genetic variation contributes to ideal CV health status in the multi-ethnic MVP cohort.Methods:Ideal CV health score was calculated based on 3 clinical factors (blood pressure, total cholesterol, and blood glucose level) and 3 behavioral factors (nonsmoking status, physical activity, and BMI). Ideal diet was not considered because only 0.4% of participants fell in the ideal diet category. GWAS was performed on continuous ideal CV health score and binary ideal CV health status using linear and logistic regression, respectively.Results:The cohort was comprised of a total of 142,404 participants (including 119,129 of European American and 16,495 of African American descent). 4.2% of the overall population had ideal CV health status based on the clinical and behavioral factors. The majority of MVP participants were older (? 60 years) and male (92.7%). In the trans-ethnic meta-analysis, we discovered 17 genome-wide significant loci associated with ideal CV health score, including APOE,transcription factor 7 like 2 (TCF7L2),fat mass and obesity-associated protein (FTO),low density lipoprotein receptor (LDLR), and proprotein convertase subtilisin/kexin type 9 (PCSK9). The protective variant in these loci had known associations with one or more components of the score, particularly lower total cholesterol and BMI. 76% of the top single nucleotide polymorphisms from GWAS of the ideal CV health score were associated with ideal CV health status at Bonferroni significance level (P<0.003).Conclusions:We identified a set of genetic variants of high interest for contributing to maintenance of ideal CV health in Veterans. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
