通过观察性和基因分析得出的2型糖尿病与中风之间关系的更多证据
Additional Evidence for the Relationship Between Type 2 Diabetes and Stroke Through Observational and Genetic Analyses.
作者信息
Zhang Wenqiang, Zhang Li, Zhu Jingwei, Xiao Chenghan, Cui Huijie, Yang Chao, Yan Peijing, Tang Mingshuang, Wang Yutong, Chen Lin, Liu Yunjie, Zou Yanqiu, Wu Xueyao, Zhang Ling, Yang Chunxia, Yao Yuqin, Li Jiayuan, Liu Zhenmi, Jiang Xia, Zhang Ben
机构信息
Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China-Peking Union Medical College C.C. Chen Institute of Health, West China School of Public Health, and West China Fourth Hospital, Sichuan University, Chengdu.
Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
出版信息
Diabetes. 2023 Nov 1;72(11):1671-1681. doi: 10.2337/db22-0954.
While type 2 diabetes mellitus (T2DM) is commonly considered a putative causal risk factor for stroke, the effect of stroke on T2DM remains unclear. The intrinsic link underlying T2DM and stroke has not been thoroughly examined. We aimed to evaluate the phenotypic and genetic relationships underlying T2DM and stroke. We evaluated phenotypic associations using data from the UK Biobank (N = 472,050). We then investigated genetic relationships by leveraging genomic data in European ancestry for T2DM, with and without adjusting (adj) for BMI (T2DM: n = 74,124 case subjects/824,006 control subjects; T2DMadjBMI: n = 50,409 case subjects/523,897 control subjects), and for stroke (n = 73,652 case subjects/1,234,808 control subjects). We performed additional analyses using genomic data in East Asian ancestry for T2DM (n = 77,418 case subjects/356,122 control subjects) and for stroke (n = 27,413 case subjects/237,242 control subjects). Observational analyses suggested a significantly increased hazard of stroke among individuals with T2DM (hazard ratio 2.28 [95% CI 1.97-2.64]), but a slightly increased hazard of T2DM among individuals with stroke (1.22 [1.03-1.45]) which attenuated to 1.14 (0.96-1.36) in sensitivity analysis. A positive global T2DM-stroke genetic correlation was observed (rg = 0.35; P = 1.46 × 10-27), largely independent of BMI (T2DMadjBMI-stroke: rg = 0.27; P = 3.59 × 10-13). This was further corroborated by 38 shared independent loci and 161 shared expression-trait associations. Mendelian randomization analyses suggested a putative causal effect of T2DM on stroke in Europeans (odds ratio 1.07 [95% CI 1.06-1.09]), which remained significant in East Asians (1.03 [1.01-1.06]). Conversely, despite a putative causal effect of stroke on T2DM also observed in Europeans (1.21 [1.07-1.37]), it attenuated to 1.04 (0.91-1.19) in East Asians. Our study provides additional evidence to underscore the significant relationship between T2DM and stroke.
虽然2型糖尿病（T2DM）通常被认为是中风的一个假定因果风险因素，但中风对T2DM的影响仍不明确。T2DM和中风之间的内在联系尚未得到充分研究。我们旨在评估T2DM和中风之间的表型和遗传关系。我们使用英国生物银行（N = 472,050）的数据评估表型关联。然后，我们通过利用欧洲血统的基因组数据研究T2DM与中风的遗传关系，对体重指数（BMI）进行了调整（T2DM：n = 74,124例/824,006对照；T2DMadjBMI：n = 50,409例/523,897对照），以及中风（n = 73,652例/1,234,808对照）。我们使用东亚血统的T2DM（n = 77,418例/356,122对照）和中风（n = 27,413例/237,242对照）的基因组数据进行了额外分析。观察性分析表明，T2DM患者中风风险显著增加（风险比2.28 [95% CI 1.97 - 2.64]），但中风患者患T2DM的风险略有增加（1.22 [1.03 - 1.45]），在敏感性分析中降至1.14（0.96 - 1.36）。观察到T2DM与中风之间存在正的总体遗传相关性（rg = 0.35；P = 1.46 × 10 - 27），很大程度上独立于BMI（T2DMadjBMI - 中风：rg = 0.27；P = 3.59 × 10 - 13）。这得到了38个共享独立基因座和161个共享表达 - 性状关联的进一步证实。孟德尔随机化分析表明，在欧洲人中T2DM对中风有假定的因果效应（优势比1.07 [95% CI 1.06 - 1.09]），在东亚人中仍然显著（1.03 [1.01 - 1.06]）。相反，尽管在欧洲人中也观察到中风对T2DM有假定的因果效应（1.21 [1.07 - 1.37]），但在东亚人中降至1.04（0.91 - 1.19）。我们的研究提供了更多证据来强调T2DM和中风之间的重要关系。
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