Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis.
Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis.
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DOI：
10.1161/strokeaha.121.034747
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发表时间：
2021-08
期刊：
影响因子：
8.3
通讯作者：
Gill D
中科院分区：
文献类型：
--
作者：
Fatumo S;Karhunen V;Chikowore T;Sounkou T;Udosen B;Ezenwa C;Nakabuye M;Soremekun O;Daghlas I;Ryan DK;Taylor A;Mason AM;Damrauer SM;Vujkovic M;Keene KL;Fornage M;Järvelin MR;Burgess S;Gill D
代谢特征会影响缺血性中风 (IS) 风险，但不同种族血统之间的差异程度尚不清楚。我们的目的是应用孟德尔随机化来研究 2 型糖尿病 (T2DM) 易感性和血脂特征对非洲血统个体 IS 风险的因果影响，并将其与欧洲血统个体中获得的估计值进行比较。对于非洲血统个体，T2DM 易感性和循环脂质的遗传代理是通过对非洲慢性病研究伙伴关系研究、英国生物银行和百万退伍军人计划（总计 N=77,061）的荟萃分析获得的。 IS 风险的遗传关联估计来自少数民族中风全基因组关联研究联盟（3,734 例病例和 18,317 例对照）。对于欧洲血统个体，相同代谢特征的遗传代理来自百万退伍军人计划（血脂 N=297,626，T2DM N=148,726 例和 965,732 名对照），IS 风险的遗传关联估计来自 MEGASTROKE 研究（34,217 名病例和 406,111 名对照）。随机效应逆方差加权孟德尔随机化被用作主要方法，并辅以对多效性更稳健的敏感性分析。较高的遗传代理 T2DM 倾向、低密度脂蛋白胆固醇 (LDL-C)、总胆固醇 (TC) 和较低的遗传代理高密度脂蛋白胆固醇 (HDL-C) 与非洲血统个体的 IS 风险增加相关（T2DM 倾向几率加倍的比值比 [95% 置信区间] 1.09 [1.07-1.11]；每增加 LDL-C 标准差： 1.12[1.04-1.21]；TC：1.23[1.06-1.43]；HDL-C：0.93[0.89-0.99]。在对欧洲血统个体进行分析时，没有证据表明这些估计存在差异。我们的分析支持 T2DM 倾向和血脂特征对非洲血统个体 IS 风险的因果影响，MR 估计值与欧洲血统个体中获得的相似。
Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes mellitus (T2DM) liability and lipid traits on IS risk in African ancestry individuals, and to compare them to estimates obtained in European ancestry individuals. For African ancestry individuals, genetic proxies for T2DM liability and circulating lipids were obtained from a meta-analysis of the African Partnership for Chronic Disease Research study, the UK Biobank and the Million Veteran Program (total N=77,061). Genetic association estimates for IS risk were obtained from the Consortium of Minority Population Genome-Wide Association Studies of Stroke (3,734 cases and 18,317 controls). For European ancestry individuals, genetic proxies for the same metabolic traits were obtained from Million Veteran Program (lipids N=297,626, T2DM N=148,726 cases and 965,732 controls), and genetic association estimates for IS risk were obtained from the MEGASTROKE study (34,217 cases and 406,111 controls). Random-effects inverse-variance weighted Mendelian randomization was used as the main method, complemented with sensitivity analyses more robust to pleiotropy. Higher genetically proxied T2DM liability, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and lower genetically proxied high-density lipoprotein cholesterol (HDL-C) were associated with increased risk of IS in African ancestry individuals (odds ratio per doubling the odds of T2DM liability [95% confidence interval] 1.09 [1.07-1.11]; per standard-deviation increase in LDL-C: 1.12 [1.04-1.21]; TC: 1.23 [1.06-1.43]; HDL-C: 0.93 [0.89-0.99]). There was no evidence for differences in these estimates when performing analyses in European ancestry individuals. Our analyses support a causal effect of T2DM liability and lipid traits on IS risk in African ancestry individuals, with MR estimates similar to those obtained in European ancestry individuals.