Shendre Aditi, Irvin Marguerite R, Wiener Howard, Zhi Degui, Limdi Nita A, Overton Edgar T, Shrestha Sadeep
Department of Epidemiology, University of Alabama at Birmingham, AL.
Department of Biostatistics, University of Alabama at Birmingham, AL.
J Am Heart Assoc. 2017 Apr 10;6(4):e004739. doi: 10.1161/JAHA.116.004739.
Local ancestry in relation to clinical cardiovascular events (CVEs) among African Americans can provide insight into their genetic susceptibility to the disease.
We examined local European ancestry (LEA) association with CVEs among 3000 African Americans from the Atherosclerosis Risk in Communities Study (ARIC). We estimated LEA using ocal ncestry Inference in adixed opulations using inkage isequilibrium (LAMP-LD) and examined its association with myocardial infarction, stroke, coronary heart disease and its composite and cardiovascular disease composite using logistic regression. Genome-wide significance was achieved by 121 LEA regions in relation to myocardial infarction and 2 in relation to the cardiovascular disease composite. The LEA region downstream of 4q32.1 was significantly associated with 2 times higher odds of myocardial infarction (=1.45×10). The LEA region upstream of 6q11.1 was associated with 0.37 times lower odds of fatal coronary heart disease (=7.34×10), whereas the LEA region downstream of 21q21.1 was associated with 1.55 times higher odds of composite coronary heart disease (3.45×10). Association of LEA with stroke was observed in the region upstream of 6p22.3 with a 1.57 times higher odds of stroke (=9.69×10). Likewise, the LEA region on 4q32.3 was associated with a 1.53 times higher odds of composite cardiovascular disease (3.04×10). We also found 20 of the LEA regions at previously significant cardiovascular disease single-nucleotide polymorphisms to be associated with CVE in our study.
Future studies are needed to replicate and/or determine the causal variants driving our associations and explore clinical applications for those consistently associated with CVEs.
非裔美国人的局部血统与临床心血管事件（CVE）的关系能够为了解其对该疾病的遗传易感性提供线索。
我们在社区动脉粥样硬化风险研究（ARIC）中的3000名非裔美国人中研究了局部欧洲血统（LEA）与CVE的关联。我们使用连锁不平衡的混合人群局部血统推断法（LAMP-LD）估计LEA，并通过逻辑回归分析其与心肌梗死、中风、冠心病及其综合指标以及心血管疾病综合指标的关联。在与心肌梗死相关的121个LEA区域和与心血管疾病综合指标相关的2个区域达到了全基因组显著性。4q32.1下游的LEA区域与心肌梗死的患病几率高出2倍显著相关（=1.45×10）。6q11.1上游的LEA区域与致命性冠心病的患病几率低0.37倍相关（=7.34×10），而21q21.1下游的LEA区域与冠心病综合指标的患病几率高出1.55倍相关（3.45×10）。在6p22.3上游区域观察到LEA与中风相关，中风患病几率高出1.57倍（=9.69×10）。同样，4q32.3上的LEA区域与心血管疾病综合指标的患病几率高出1.53倍相关（3.04×10）。我们还发现，在我们的研究中，先前显著的心血管疾病单核苷酸多态性中的20个LEA区域与CVE相关。
未来需要开展研究以重复和/或确定驱动我们所发现关联的因果变异，并探索那些与CVE持续相关的变异的临床应用。
