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首页> 外文期刊>Circulation. Genomic and precision medicine. >Associations of Genetically Predicted Lp(a) (Lipoprotein [a]) Levels With Cardiovascular Traits in Individuals of European and African Ancestry
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Associations of Genetically Predicted Lp(a) (Lipoprotein [a]) Levels With Cardiovascular Traits in Individuals of European and African Ancestry

机译:关联的基因预测Lp (a)(脂蛋白[a])水平与心血管欧洲和非洲的特征的个体祖先

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BACKGROUND: Lp(a) (li poprotein [a]) levels are higher in individuals of African ancestry (AA) than in individuals of European ancestry (EA). We examined associations of genetically predicted Lp(a) levels with (1) atherosclerotic cardiovascular disease subtypes: coronary heart disease, cerebrovascular disease, peripheral artery disease, and abdominal aortic aneurysm and (2) nonatherosclerotic cardiovascular disease phenotypes, stratified by ancestry. METHODS: We performed (1) Mendelian randomization analyses for previously reported cardiovascular associations and (2) Mendelian randomization-phenome-wide association analyses for novel associations. Analyses were stratified by ancestry in electronic Medical Records and Genomics, United Kingdom Biobank, and Million Veteran Program cohorts separately and in a combined cohort of 804 507 EA and 103 580 AA participants. RESULTS: In Mendelian randomization analyses using the combined cohort, a 1-SD genetic increase in Lp(a) level was associated with atherosclerotic cardiovascular disease subtypes in EA—odds ratio and 95% CI for coronary heart disease 1.28 (1.16-1.41); cerebrovascular disease 1.14 (1.07-1.21); peripheral artery disease 1.22 (1.11-1.34); abdominal aortic aneurysm 1.28 (1.17-1.40); in AA, the effect estimate was lower than in EA and nonsignificant for coronary heart disease 1.11 (0.99-1.24) and cerebrovascular disease 1.06 (0.99-1.14) but similar for peripheral artery disease 1.16 (1.01-1.33) and abdominal aortic aneurysm 1.34 (1.11-1.62). In EA, a 1-SD genetic increase in Lp(a) level was associated with aortic valve disorders 1.34 (1.10-1.62), mitral valve disorders 1.18 (1.09-1.27), congestive heart failure 1.12 (1.05-1.19), and chronic kidney disease 1.07 (1.01-1.14). In AA, no significant associations were noted for aortic valve disorders 1.08 (0.941.25), mitral valve disorders 1.02 (0.89-1.16), congestive heart failure 1.02 (0.95-1.10), or chronic kidney disease 1.05 (0.99-1.12). Mendelian randomization-phenome-wide association analyses identified novel associations in EA with arterial thromboembolic disease, nonaortic aneurysmal disease, atrial fibrillation, cardiac conduction disorders, and hypertension. CONCLUSIONS: Many cardiovascular associations of genetically increased Lp(a) that were significant in EA were not significant in AA. Lp(a) was associated with atherosclerotic cardiovascular disease in four major arterial beds in EA but only with peripheral artery disease and abdominal aortic aneurysm in AA. Additionally, novel cardiovascular associations were detected in EA.
机译:背景:Lp (a)(李poprotein [a])水平高个人的非洲血统(AA)个人(EA)的欧洲血统。检查关联基因预测Lp (a)水平与(1)动脉粥样硬化心血管疾病亚型:冠心病疾病、脑血管疾病、周围和腹主动脉瘤和动脉疾病(2) nonatherosclerotic心血管疾病表型,分层的祖先。(1)执行孟德尔随机化分析为之前报道心血管协会和(2)孟德尔randomization-phenome-wide关联分析小说协会。电子医疗记录和祖先基因组学、英国生物库和百万分开人群,在资深项目结合群804 507 EA和103 580 AA参与者。使用队列相结合,分析1-SD基因增加Lp (a)水平有关与动脉粥样硬化性心血管疾病亚型为冠状动脉EA-odds比和95%可信区间心脏病1.28 (1.16 - -1.41);疾病为1.14 (1.07 - -1.21);疾病为1.22 (1.11 - -1.34);动脉瘤1.28 (1.17 - -1.40);估计是低于EA和无意义的对于冠心病1.11 (0.99 - -1.24)脑血管疾病1.06 (0.99 - -1.14)类似的外周动脉疾病1.161.34(1.01 - -1.33)和腹主动脉瘤(1.11 - -1.62)。Lp (a)水平与主动脉瓣障碍1.34(1.10 - -1.62),二尖瓣障碍1.18(1.09 - -1.27),充血性心力失败的1.12(1.05 - -1.19),和慢性肾脏疾病1.07(1.01 - -1.14)。协会以主动脉瓣障碍1.08(0.941.25),二尖瓣疾病1.02(0.89 - -1.16), 1.02充血性心力衰竭1.05(0.95 - -1.10),或慢性肾脏疾病(0.99 - -1.12)。关联分析确定了小说协会在EA与动脉血栓栓塞动脉瘤性疾病,疾病,nonaortic心房纤维性颤动、心脏传导障碍,高血压关联的基因增加Lp (a)在EA并不重要重要AA。心血管疾病在四个主要的动脉床在EA只是与外周动脉疾病和腹主动脉瘤在AA。此外,小说心血管协会在EA发现。

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