Shendre Aditi, Wiener Howard, Irvin Marguerite R, Zhi Degui, Limdi Nita A, Overton Edgar T, Wassel Christina L, Divers Jasmin, Rotter Jerome I, Post Wendy S, Shrestha Sadeep
Circ Cardiovasc Genet. 2017 Apr;10(2). doi: 10.1161/CIRCGENETICS.116.001569.
Local ancestry may contribute to the disproportionate burden of subclinical and clinical cardiovascular disease among admixed African Americans compared with other populations, suggesting a rationale for admixture mapping.
We estimated local European ancestry (LEA) using Local Ancestry inference in adMixed Populations using Linkage Disequilibrium method (LAMP-LD) and evaluated the association with common carotid artery intima-media thickness (cCIMT) using multivariable linear regression analysis among 1554 African Americans from MESA (Multi-Ethnic Study of Atherosclerosis). We conducted secondary analysis to examine the significant cCIMT-LEA associations with clinical cardiovascular disease events. We observed genome-wide significance in relation to cCIMT association with the gene (secretion-regulating guanine nucleotide exchange factor; β=0.0137; =2.98×10), also associated with higher odds of stroke (odds ratio=1.71; =0.02). Several regions, in particular gene (Ca-dependent secretion activator 1) region identified in MESA, were also replicated in the ARIC cohort (Atherosclerosis Risk in Communities). We observed other cCIMT-LEA regions associated with other clinical events, most notably the regions harboring gene (creatine kinase, mitochondrial 2) and gene (Ras protein-specific guanine nucleotide-releasing factor 2) with all clinical events except stroke, the gene (leucine-rich repeat containing 3B) with myocardial infarction, the gene (protein arginine methyltransferase 3) with stroke, and the gene (lipoma high mobility group protein I-C fusion partner-like 2) with hard and all coronary heart disease.
We identified several novel LEA regions, in addition to previously identified genetic variations, associated with cCIMT and cardiovascular disease events among African Americans.
与其他人群相比，局部血统可能导致非裔美国人在亚临床和临床心血管疾病负担方面存在不成比例的情况，这为混合映射提供了理论依据。
我们使用连锁不平衡方法在混合人群中进行局部血统推断（LAMP-LD）来估计局部欧洲血统（LEA），并在来自动脉粥样硬化多族裔研究（MESA）的1554名非裔美国人中，使用多变量线性回归分析评估其与颈总动脉内膜中层厚度（cCIMT）的关联。我们进行了二次分析，以检验cCIMT-LEA与临床心血管疾病事件之间的显著关联。我们观察到与cCIMT关联在全基因组范围内具有显著性的基因（分泌调节鸟嘌呤核苷酸交换因子；β=0.0137；P=2.98×10），该基因也与中风几率较高相关（比值比=1.71；P=0.02）。在MESA中确定的几个区域，特别是基因（钙依赖性分泌激活因子1）区域，在社区动脉粥样硬化风险（ARIC）队列中也得到了重复验证。我们观察到其他与其他临床事件相关的cCIMT-LEA区域，最显著的是携带基因（线粒体肌酸激酶2）和基因（Ras蛋白特异性鸟嘌呤核苷酸释放因子2）的区域与除中风外的所有临床事件相关，基因（富含亮氨酸重复序列3B）与心肌梗死相关，基因（蛋白质精氨酸甲基转移酶3）与中风相关，基因（脂肪瘤高迁移率族蛋白I-C融合伴侣样2）与硬性和所有冠心病相关。
除了先前确定的基因变异外，我们还在非裔美国人中确定了几个与cCIMT和心血管疾病事件相关的新的LEA区域。
