Causal associations between CD40/CD40L and aortic diseases: A mendelian randomization study.
Causal associations between CD40/CD40L and aortic diseases: A mendelian randomization study.
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CD40/CD40L 与主动脉疾病之间的因果关系：孟德尔随机研究
DOI：
10.3389/fgene.2022.998525
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发表时间：
2022
影响因子：
3.7
通讯作者：
Guo, Xiaogang
中科院分区：
文献类型：
--
作者：
Cui, Xiao;Xuan, Tianming;Chen, Siyuan;Guo, Xiaogang
背景资料：CD 40和CD 40 L与主动脉夹层（AD）和主动脉瘤（AA）相关，但其因果关系尚未确定。 研究方法：我们进行了一项双样本孟德尔随机化（MR）研究，以评估CD 40/CD 40 L与主动脉疾病（包括AD和AA）之间的因果关系。CD 40和CD 40 L的工具变量（IV）选自由涉及30，931名欧洲血统个体的基因组研究发布的高质量蛋白质数量性状基因座数据集。AD和AA的全基因组关联研究汇总统计数据来自FinnGen Release 7，所有关注结果的对照为288638例，AD为680例，AA为6，092例，也来自欧洲血统。对于AA亚型，分别有5，881例胸AA（TAA）和2，434例腹AA（AAA）。采用方差加权和Wald比计算因果估计。水平多效性和异质性分别采用MR-Egger回归分析和Cochran Q检验进行评估。进一步进行了留一分析。 结果：筛选出3个CD 40单核苷酸多态性（SNP）和1个CD 40 L单核苷酸多态性（SNP）。我们发现，遗传性CD 40水平与AD（比值比[OR]：0.777，95%置信区间[CI]：0.618-0.978，p = 0.031）和AA（OR：0.905，95% CI：0.837-0.978，p = 0.012）的风险呈负相关，在TAA中一致（均p < 0.050）。存在CD 40 L时AD和AA风险增加的趋势，但未达到统计学显著性。未观察到显著的水平多效性或异质性。 结论：我们的MR研究提供了证据支持CD 40与AD和AA风险降低之间的因果关系。
Background: CD40 and CD40L have been reported as associated with aortic dissection (AD) and aortic aneurysm (AA), but the causality of the associations has not been established yet. Methods: We conducted a two-sample Mendelian randomization (MR) study to assess the causal inference between CD40/CD40L and aortic diseases including AD and AA. The instrumental variables (IVs) for CD40 and CD40L were selected from a high-quality protein quantitative trait loci dataset released by a genomic study involving 30,931 individuals of European ancestry. The genome-wide association studies summary statistics for AD and AA were from the FinnGen Release 7, with 288638 controls for all outcomes of interests, 680 cases for AD and 6,092 cases for AA, also from European ancestry. For AA subtypes, there were 5,881 cases of thoracic AA (TAA) and 2,434 cases of abdominal AA (AAA) respectively. Inverse-variance weighted and Wald ratio were applied for calculating causal estimates. Horizontal pleiotropy and heterogeneity were assessed using MR-Egger regression analysis and Cochran Q test, respectively. Leave-one-out analyses were further performed. Results: Three single-nucleotide polymorphisms (SNPs) for CD40 and one SNP for CD40L were selected as IVs. We found genetic proxied CD40 levels inversely associated with the risk of AD (odds ratio [OR]: 0.777, 95% confidence interval [CI]: 0.618–0.978, p = 0.031) and AA (OR: 0.905, 95% CI: 0.837–0.978, p = 0.012), consistent across TAA (both p < 0.050). There were trends of increased risks of AD and AA in the presence of CD40L while not reaching statistical significance. No significant horizontal pleiotropy or heterogeneity was observed. Conclusion: Our MR study provides evidence supporting the causal association between CD40 and the reduced risks of both AD and AA.
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影响因子：
7.7
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
通讯作者：
Thompson JR
DOI：
10.1161/atvbaha.120.313991
发表时间：
2020-03-01
影响因子：
8.7
作者：
Shen, Ying H.;LeMaire, Scott A.;Lu, Hong S.
通讯作者：
Lu, Hong S.
影响因子：
6
作者：
Touat, Z;Ollivier, V;Michel, JB
通讯作者：
Michel, JB
影响因子：
39.3
作者：
Erbel, Raimund;Aboyans, Victor;Vrints, Christiaan J. M.
通讯作者：
Vrints, Christiaan J. M.
DOI：
10.18632/aging.101651
发表时间：
2018-11-16
期刊：
Aging
影响因子：
--
作者：
Han L;Dai L;Zhao YF;Li HY;Liu O;Lan F;Jiang WJ;Zhang HJ
通讯作者：
Zhang HJ