[具体内容]与冠状动脉钙化的关联因性别和吸烟情况而异。
Association of with Coronary Artery Calcium Differs by Sex and Cigarette Smoking.
作者信息
Voorhies Kirsten, Young Kendra, Hsu Fang-Chi, Palmer Nicholette D, McDonald Merry-Lynn N, Lee Sanghun, Hahn Georg, Hecker Julian, Prokopenko Dmitry, Wu Ann Chen, Regan Elizabeth A, DeMeo Dawn, Kinney Greg L, Crapo James D, Cho Michael H, Silverman Edwin K, Lange Christoph, Budoff Matthew J, Hokanson John E, Lutz Sharon M
机构信息
Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, MA 02115, USA.
Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
出版信息
J Cardiovasc Dev Dis. 2024 Jun 27;11(7):194. doi: 10.3390/jcdd11070194.
Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and is a complex heritable trait with both genetic and environmental risk factors, including sex and smoking. We performed genome-wide association (GWA) analyses for CAC among all participants and stratified by sex in the COPDGene study ( = 6144 participants of European ancestry and = 2589 participants of African ancestry) with replication in the Diabetes Heart Study (DHS). We adjusted for age, sex, current smoking status, BMI, diabetes, self-reported high blood pressure, self-reported high cholesterol, and genetic ancestry (as summarized by principal components computed within each racial group). For the significant signals from the GWA analyses, we examined the single nucleotide polymorphism (SNP) by sex interactions, stratified by smoking status (current vs. former), and tested for a SNP by smoking status interaction on CAC. We identified genome-wide significant associations for CAC in the chromosome 9p21 region [] among all COPDGene participants ( = 7.1 × 10) and among males ( = 1.0 × 10), but the signal was not genome-wide significant among females ( = 6.4 × 10). For the sex stratified GWA analyses among females, the chromosome 6p24 region [] had a genome-wide significant association ( = 4.4 × 10) with CAC, but this signal was not genome-wide significant among all COPDGene participants ( = 1.7 × 10) or males ( = 0.03). There was a significant interaction for the SNP rs9349379 in with sex ( = 0.02), but the interaction was not significant for the SNP rs10757272 in with sex ( = 0.21). In addition, had a stronger association with CAC among current smokers ( = 6.2 × 10) than former smokers ( = 7.5 × 10) and the SNP by smoking status interaction was marginally significant ( = 0.03). had a strong association with CAC among both former ( = 7.7 × 10) and current smokers ( 1.7 × 10) and the SNP by smoking status interaction was not significant ( 0.40). Among current and former smokers of European ancestry in the COPDGene study, we identified a genome-wide significant association in the chromosome 6p24 region [] with CAC among females, but not among males. This region had a significant SNP by sex and SNP by smoking interaction on CAC.
冠状动脉钙化（CAC）是亚临床动脉粥样硬化的一个标志物，是一种具有遗传和环境风险因素（包括性别和吸烟）的复杂遗传性状。在慢性阻塞性肺疾病基因（COPDGene）研究（n = 6144名欧洲血统参与者和n = 2589名非洲血统参与者）中，我们对所有参与者以及按性别分层后的参与者进行了CAC的全基因组关联（GWA）分析，并在糖尿病心脏研究（DHS）中进行了重复验证。我们对年龄、性别、当前吸烟状况、体重指数、糖尿病、自我报告的高血压、自我报告的高胆固醇以及遗传血统（由每个种族群体内计算的主成分总结）进行了调整。对于GWA分析中的显著信号，我们按性别交互作用检查单核苷酸多态性（SNP），按吸烟状况（当前吸烟者与既往吸烟者）分层，并测试SNP与吸烟状况对CAC的交互作用。我们在所有COPDGene参与者（P = 7.1×10⁻⁸）和男性（P = 1.0×10⁻⁸）中确定了9号染色体p21区域与CAC的全基因组显著关联，但在女性中该信号未达到全基因组显著水平（P = 6.4×10⁻⁵）。对于女性中的性别分层GWA分析，6号染色体p24区域（P = 4.4×10⁻⁸）与CAC存在全基因组显著关联，但在所有COPDGene参与者（P = 1.7×10⁻⁵）或男性中该信号未达到全基因组显著水平（P = 0.03）。rs9349379 SNP与性别存在显著交互作用（P = 0.02），但rs10757272 SNP与性别不存在显著交互作用（P = 0.21）。此外，rs9349379在当前吸烟者中与CAC的关联（P = 6.2×10⁻⁸）比在既往吸烟者中更强（P = 7.5×10⁻⁵），且SNP与吸烟状况的交互作用接近显著（P = 0.03）。rs10757272在既往吸烟者（P = 7.7×10⁻⁸）和当前吸烟者（P = 1.7×10⁻⁵）中均与CAC有强关联，且SNP与吸烟状况的交互作用不显著（P = 0.40）。在COPDGene研究中欧洲血统的当前吸烟者和既往吸烟者中，我们在6号染色体p24区域确定了女性中与CAC的全基因组显著关联，但男性中未发现。该区域在CAC上存在SNP与性别以及SNP与吸烟的显著交互作用。
Zotero 插件