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山东大学学报 (医学版) ›› 2023, Vol. 61 ›› Issue (5): 102-107.doi: 10.6040/j.issn.1671-7554.0.2023.0085

• 公共卫生与管理学 • 上一篇    下一篇

氨基酸与2型糖尿病因果关系的孟德尔随机化分析

张天鑫1,2,张婷3,黄鑫1,2,韩佳沂1,2,王淑康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.山东省公共卫生临床中心药学部, 山东 济南 250102
  • 发布日期:2023-05-15
  • 通讯作者: 王淑康. E-mail:wsk2001@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(82173624,81872712);山东省自然科学基金(ZR2019ZD02)

A mendelian randomization analysis on the causal associations between amino acids and type 2 diabetes

ZHANG Tianxin1,2, ZHANG Ting3, HUANG Xin1,2, HAN Jiayi1,2, WANG Shukang1,2   

  1. 1. Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Institute of Medical Dataology, Shandong University, Jinan 250002, Shandong, China;
    3. Department of Pharmacy, Shandong Public Health Clinical Center, Jinan 250102, Shandong, China
  • Published:2023-05-15

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摘要： 目的 探讨氨基酸与2型糖尿病(T2D)的双向因果关联。 方法 利用氨基酸和T2D全基因组关联研究汇总数据,通过逆方差加权法、加权中位数法、MR-Egger回归法、MR稳健调整轮廓得分法、MR多效性残差及异质性检测法(MR-PRESSO)进行两样本双向孟德尔随机化(MR)分析,并采用Cochrans Q检验、MR-Egger回归截距项检验、MR-PRESSO全局检验评估结果的异质性和水平多效性。 结果 逆方差加权法结果显示,亮氨酸(OR=1.239,95%CI: 1.078~1.424,P=0.002 5)、缬氨酸(OR=1.222,95%CI: 1.071~1.394,P=0.002 9)会增加T2D发病风险,甘氨酸(OR=0.885,95%CI: 0.831~0.942,P=0.000 1)则降低T2D发病风险。反向MR分析结果显示,T2D分别与亮氨酸、异亮氨酸、缬氨酸、丙氨酸、苯丙氨酸、酪氨酸的增加和甘氨酸的降低有因果关联。多种MR方法的结果基本一致,且敏感性分析未发现潜在的多效性。 结论 较高水平的亮氨酸、缬氨酸及较低水平的甘氨酸与T2D发病风险具有双向因果关联,T2D对异亮氨酸、丙氨酸、苯丙氨酸、酪氨酸有正向因果效应。

关键词: 氨基酸, 2型糖尿病, 孟德尔随机化, 因果推断, 支链氨基酸

Abstract: Objective To investigate the bidirectional causal association between amino acids and type 2 diabetes(T2D). Methods Data of genome-wide association study on amino acids and T2D were collected. Inverse variance weighted method, weighted median method, MR-Egger regression method, MR robust adjusted profile score method and MR pleiotropy residual sum and outlier method(MR-PRESSO)were adopted for two-sample bidirectional mendelian randomization(MR)analysis. Cochrans Q test, MR-Egger intercept test, and MR-PRESSO global test were used to evaluate the heterogeneity and pleiotropy of the results. Results The results of inverse variance weighted method showed that leucine(OR=1.239, 95%CI: 1.078-1.424, P=0.002 5)and valine(OR=1.222, 95%CI: 1.071-1.394, P=0.002 9)increased the risk of T2D, while glycine(OR=0.885, 95%CI: 0.831-0.942, P=0.000 1)decreased the risk. The results of reverse MR analysis showed that the risk of T2D was causally associated with increased leucine, isoleucine, valine, alanine, phenylalanine and tyrosine, and decreased glycine. The results of multiple MR methods suggested robustness of causal associations and no potential pleiotropy was found in the sensitivity analysis. Conclusion Higher levels of leucine and valine and lower level of glycine have bidirectional causal associations with T2D risk. T2D has positive causal effects on isoleucine, alanine, phenylalanine and tyrosine.

Key words: Amino acids, Type 2 diabetes, Mendelian randomization, Causal inference, Branched-chain amino acids

中图分类号: 

  • R587.1
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