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山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (5): 107-114.doi: 10.6040/j.issn.1671-7554.0.2019.721

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基于两样本孟德尔随机化的身高和冠心病风险之间因果关系

李云霞1,2,李洪凯1,2,马韫韬3,于媛媛1,2,孙晓茹1,2,刘新辉1,2, 司书成1,2,侯蕾1,2,袁同慧1,2,刘璐1,2,李文超1,2,薛付忠1,2,刘言训1,2   

  1. 1. 山东大学齐鲁医学院公共卫生学院生物统计学系，山东 济南 250012；2. 山东大学健康医疗大数据研究院，山东 济南 250002； 3. 兰州大学第二临床医学院，甘肃 兰州 730030
  • 发布日期:2022-09-27
  • 通讯作者: 刘言训. E-mail: liu-yx@sdu.edu.cn薛付忠. E-mail: xuefzh@sdu.edu.cn

Causal association between height and risk of coronary heart disease: a two-sample Mendelian randomization analysis

LI Yunxia1,2, LI Hongkai1,2, MA Yuntao3, YU Yuanyuan1,2, SUN Xiaoru1,2, LIU Xinhui1,2, SI Shucheng1,2, HOU Lei1,2, YUAN Tonghui1,2, LIU Lu1,2, LI Wenchao1,2, XUE Fuzhong1,2, LIU Yanxun1,2   

  • Published:2022-09-27

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摘要： 目的 采用孟德尔随机化方法探讨身高和冠心病之间的因果关系。 方法 对基于全基因关联研究(GWAS)的Meta分析数据进行二次数据分析。利用大样本GWAS汇总数据,选择与身高密切相关的遗传位点作为工具变量,分别用逆方差加权法、加权中位数法和MR-Egger回归作两样本孟德尔随机化分析,以OR值评价身高与冠心病之间的因果关系。 结果 共纳入108个SNP位点作为工具变量,随机效应逆方差加权法和加权中位数法估计得OR值分别为0.760 5(0.644 8~0.896 9)和0.737 9(0.589 9~0.923 1),两种方法结果相近,均支持身高与冠心病之间存在因果关系。MR-Egger回归方程截距项为-0.003 1(-0.013 8~0.007 6),表明因果估计结果受基因多效性影响的可能性较小。身高每增加一倍标准差(SD=0.0699m),冠心病风险降低约25%。 结论 身高与冠心病之间存在负向因果关联。

关键词: 孟德尔随机化, 身高, 冠心病, 因果推断

Abstract: Objective To explore the causal relationship between height and cardiovascular heart disease(CHD)using the Mendelian randomization(MR)analysis. Methods This study was a secondary data analysis based on Meta-analysis data of Genome-Wide Association Study(GWAS). Genetic variants which were closely related to height in large sample GWAS summary data were identified as instrumental variables(IV). Using odds ratio(OR)as outcome indicator, the causal relationship between height and CHD was analyzed by two-sample MR methods, including inverse variance weighted(IVW)method, weighted median estimator(WME)method and MR-Egger regression. Results A total of 108 SNPs were chosen as IV. The OR and 95%CI between height and CHD were estimated to be 0.760 5(0.644 8-0.896 9)and 0.737 9(0.589 9-0.923 1)by IVW and WME methods, respectively. The results were similar, and suggested a causal relationship between height and CHD. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results(the intercept was -0.003 1, 95%CI: -0.013 8-0.0076). The risk of CHD decreased by about 25% when height increase one standard deviation(SD=0.0699 m). Conclusion There is a negative causal relationship between height and CHD.

Key words: Mendelian randomization, Height, Cardiovascular heart disease, Causal inference

中图分类号: 

  • R541.4
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