Albumin and infection following a procedure: a Mendelian Randomization study

Abstract Background Serum albumin concentration had been proposed to be an important changeable factor increasing the risk of infection following a procedure, and a perioperative albumin supplementation was recommended in some clinical scenarios. However, the results of the published epidemiological observational studies on these hypotheses are still inconclusive. Here, we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal effect of albumin on infection following a procedure using publically available genome-wide association studies (GWAS) summary statistics. Methods A series of quality control steps were taken in our analysis to select eligible instrumental single nucleotide polymorphisms (SNPs) which were strongly associated with exposure. To make the conclusions more robust and reliable, we utilized several robust analytical methods (inverse-variance weighted, MR-Egger regression, and Weighted median method) that are based on different assumptions of two-sample MR analysis. The Cochran’s Q test, MR- Pleiotropy RESidual Sum and Outlier (PRESSO) global test, MR-Egger intercept test, and “leave-one-out” sensitivity analysis were performed to evaluate the heterogeneity, horizontal pleiotropy, and stability of these genetic variants on outcome. Outlier variants were removed step-by-step to reduce heterogeneity and the effect of horizontal pleiotropy if identified by the MR-PRESSO outlier test. Results Our two-sample MR analysis with one group of exposure GWAS summary statistics and two groups of outcome GWAS summary statistics did not suggest the causal effect of increased/decreased albumin concentration on infection following a procedure. We did not observe the evidence of heterogeneity or directional pleiotropy. There was no potentially influential SNP driving the causal link under “leave-one-out” analysis and the result was stable. Conclusions Our MR analysis did not support the causal effect of albumin on infection following a procedure. The result was robust based on several analytical methods. Perioperative albumin supplementation was questionable and should be investigated with more randomized controlled trials.