Large-scale correlation analysis of deep venous thrombosis and gut microbiota

Abstract

Objective: Although previous studies have shown that gut microbiota may be involved in the occurrence of deep venous thrombosis (DVT), the specific link between the two remains unclear. The present study aimed to explore this question from a genetic perspective. Materials and methods: Genome-wide association study (GWAS) summary data of DVT were obtained from the UK Biobank (N = 9,059). GWAS summary data of the gut microbiota were obtained from the Flemish Gut Flora Project (N = 2,223) and two German cohorts (FoCus, N = 950; PopGen, N = 717). All the participants were of European ancestry. Linkage disequilibrium score (LDSC) regression has great potential for analyzing the heritability of disease or character traits. LDSC regression was used to analyze the genetic correlation between DVT and the gut microbiota based on the GWAS summary data obtained from previous studies. Mendelian randomization (MR) was used to analyze the genetic causal relationship between DVT and the gut microbiota. We used the random effects inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode to perform MR analysis. We performed a sensitivity analysis of the MR analysis results by examining heterogeneity and horizontal pleiotropy. Results: Linkage disequilibrium score analysis showed that Streptococcaceae (correlation coefficient = −0.542, SE = 0.237, P = 0.022), Dialister (correlation coefficient = −0.623, SE = 0.316, P = 0.049), Streptococcus (correlation coefficient = −0.576, SE = 0.264, P = 0.029), and Lactobacillales (correlation coefficient = −0.484, SE = 0.237, P = 0.042) had suggestive genetic correlation with DVT. In addition, the MR analysis showed that Streptococcaceae had a positive genetic causal relationship with DVT (P = 0.027, OR = 1.005). There was no heterogeneity or horizontal pleiotropy in the MR analysis (P > 0.05). Conclusion: In this study, four gut microbes (Streptococcaceae, Dialister Streptococcus, Lactobacillales) had suggestive genetic correlations with DVT, and Streptococcaceae had a positive causal relationship with DVT. Our findings provide a new research direction for the further study of and prevention of DVT.