Mendelian Randomization Analysis on the Causal Association Between Uric Acid-mediated Body Mass Index and Congestive Heart Failure
10.3969/j.issn.1000-3614.2024.05.011
- VernacularTitle:尿酸介导体重指数与慢性心力衰竭关系的孟德尔随机化分析
- Author:
Teng GE
1
;
Ying FANG
;
Hongfei QI
;
Bo NING
;
Yongqing WU
;
Mingjun ZHAO
Author Information
1. 陕西中医药大学第一临床医学院 中西医临床医学系,咸阳 712046
- Keywords:
body mass index;
uric acid;
congestive heart failure;
Mendelian randomization analysis;
causality;
mediating factor
- From:
Chinese Circulation Journal
2024;39(5):495-502
- CountryChina
- Language:Chinese
-
Abstract:
Objectives:To explore the causal relationship between body mass index,uric acid and congestive heart failure(CHF),and provide genetic evidence to support the association between uric acid-mediated body mass index and the risk of CHF. Methods:Using the published data set of genome-wide association studies(GWAS)in East Asia,inverse variance weighting(IVW)method was used as the main analysis method,and MR-Egger method,weighted median model(WME),simple model and weighted model were used to analyze the causal relationship between body mass index,uric acid and CHF.MR-Egger regression was used to detect pleiotropy,Cochran Q test was used to detect heterogeneity,leave-one-out sensitivity was used to detect bias,funnel plot was drawn to detect bias,and MR-PRESSO package was used to remove outlier single nucleotide polymorphism(SNP).After Mendelian analysis,the mediating effect ratio was calculated,and the reverse Mendelian randomization study results between body mass index,uric acid and CHF were analyzed. Results:IVW method showed that body mass index(OR=1.685,95%CI:1.417-2.003,P<0.001)and uric acid(OR=1.225,95%CI:1.087-1.380,P<0.001)were risk factors of CHF in two-sample Mendelian analysis.Body mass index(OR=1.204,95%CI:1.139-1.273,P<0.001)was a risk factor for uric acid.The mediating effect of uric acid was 7.23%.The P values of MR-Egger regression intercept terms were all>0.05,that is,there was no pleiotropy of the selected SNP,and the causal inference method was valid.The Cochran Q test P values of body mass index and uric acid,and body mass index and CHF were<0.01,indicating heterogeneity.IVW analysis of CHF and body mass index in reverse Mendelian analysis was OR=0.977,95%CI:0.947-1.008,P>0.05 and CHF and uric acid was OR=1.000,95%CI:0.963-1.038,P>0.05,so the reverse causal inference was not valid.However,the analysis of uric acid and body mass index showed pleiotropy,so the causal inference method was invalid. Conclusions:There is a causal and positive correlation between body mass index and CHF.There is a causal relationship and positive correlation between uric acid and CHF.However,uric acid is an incomplete mediator between body mass index and CHF.
