Serum Urate and Atrial Fibrillation: A Bidirectional Mendelian Randomization Study

Abstract

Background

Observational studies indicate that serum urate level is associated with atrial fibrillation (AF). However, whether this association is causal remains controversial, due to confounding factors and reverse causality. We aim to evaluate the causal relationship of genetically predicted serum urate level with AF.

Methods

A bidirectional Mendelian randomization (MR) study was performed. Instrumental variables were obtained from the Global Urate Genetics Consortium (110347 individuals). We obtained summary statistics of AF from two genome-wide association studies (GWAS) data sets for AF. Inverse-variance-weighted method was applied to obtain MR estimates and other statistical methods were conducted in the sensitivity analyses. The reverse MR analysis was performed to evaluate the effect of AF on serum urate levels.

Results

Genetically determined serum urate level was not associated with AF in two studies (OR, 1.03; 95% CI, 0.95–1.11; p = 0.47); (OR, 1.06; 95% CI, 0.99–1.12; p = 0.09). The main results kept robust in the most sensitivity analyses. Multivariable MR analyses suggested that the association pattern did not change, after adjusting for body mass index (BMI), HbA1c: hemoglobin A1c (HbA1c), hypertension, low-density lipoprotein cholesterol (LDL-C) and coronary heart disease. No causal effect of AF on serum urate levels was found in two studies (OR, 1.02; 95% CI, 0.98–1.05; p = 0.30); (OR, 1.00; 95% CI, 0.98–1.03; p = 0.95).

Conclusions

Our MR study supports no bidirectional causal effect of serum urate levels and AF. This implies that treatments aimed at lowering uric acid may not reduce the risk of AF.