Type 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes Mendelian randomization study
Type 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes Mendelian randomization study
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DOI：
10.1212/wnl.0000000000004173
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发表时间：
2017-08-01
期刊：
影响因子：
9.9
通讯作者：
Markus, Hugh S.
中科院分区：
文献类型：
--
作者：
Larsson, Susanna C.;Scott, Robert A.;Markus, Hugh S.
目的：应用孟德尔随机化(MR)方法确定2型糖尿病(T2D)、空腹血糖、空腹胰岛素和体重指数(BMI)是否与特定的缺血性卒中亚型存在因果关系。方法：采用逆方差加权(常规)和加权中位数方法计算各可能危险因素与缺血性卒中亚型之间的相关性，并用MR-Egger回归分析多效性。作为辅助变量的单核苷酸多态(SNPs)数目为：T2D 49个，空腹血糖36个，空腹胰岛素18个，BMI 77个。结果：常规MR分析显示，遗传预测的T2D与大动脉卒中(优势比[OR]1.28，95%可信区间[CI]1.16-1.40，p=3.3×10(-7))和小血管卒中(OR 1.21，95%CI 1.10-1.33，p=8.9×10(-5))之间存在关联，但与心栓性卒中(OR 1.06，95%可信区间为0.97-1.15，p=0.17)。在使用加权中位数方法的敏感性分析中，T2D与大动脉卒中而不是小血管卒中的关联是一致的，没有证据表明具有多效性。基因预测的空腹血糖、空腹胰岛素水平和BMI与任何缺血性卒中亚型均无统计学意义的相关性。结论：本研究支持T2D可能与大动脉卒中有因果关系。
Objective: To implement a mendelian randomization (MR) approach to determine whether type 2 diabetes mellitus (T2D), fasting glucose, fasting insulin, and body mass index (BMI) are causally associated with specific ischemic stroke subtypes.Methods: MR estimates of the association between each possible risk factor and ischemic stroke subtypes were calculated with inverse-variance weighted (conventional) and weighted median approaches, and MR-Egger regression was used to explore pleiotropy. The number of single nucleotide polymorphisms (SNPs) used as instrumental variables was 49 for T2D, 36 for fasting glucose, 18 for fasting insulin, and 77 for BMI. Genome-wide association study data of SNP-stroke associations were derived from METASTROKE and the Stroke Genetics Network (n = 18,476 ischemic stroke cases and 37,296 controls).Results: Conventional MR analysis showed associations between genetically predicted T2D and large artery stroke (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.16-1.40, p = 3.3 x 10(-7)) and small vessel stroke (OR 1.21, 95% CI 1.10-1.33, p = 8.9 x 10(-5)) but not cardioembolic stroke (OR 1.06, 95% CI 0.97-1.15, p = 0.17). The association of T2D with large artery stroke but not small vessel stroke was consistent in a sensitivity analysis using the weighted median method, and there was no evidence of pleiotropy. Genetically predicted fasting glucose and fasting insulin levels and BMI were not statistically significantly associated with any ischemic stroke subtype.Conclusions: This study provides support that T2D may be causally associated with large artery stroke.