PB0045 - Causal relationships of amino acids with coronary arterial disease, ischemic stroke and venous thromboembolism: A Mendelian randomization analysis

Background: There is an increasing recognition that amino acids (AAs) may influence the risk of cardiovascular diseases, but whether these effects are causal remains unclear.

Aims: This study aims to investigate the causal relationships between 20 AAs and the risk of three major thromboembolic diseases, including coronary arterial disease (CAD), ischemic stroke, and venous thromboembolism, using Mendelian randomization (MR) analysis.

Methods: This MR study utilized single-nucleotide polymorphisms (SNPs) significantly associated with AAs as instrumental variables. Summary-level data for all traits were obtained from published studies or the MRC Integrative Epidemiology Unit OpenGWAS data (Figure 1). Causal effects were estimated by SNP-specific Wald ratio and meta-analyzed by inverse variance weighting with multiplicative random effect.

Results: A total of 7 AAs were causally associated with the risk of thromboembolic diseases. Branched-chain AAs (leucine and isoleucine) were positively associated with the risk of thromboembolic diseases in the arterial system, while an inverse association of leucine in the venous system was observed. Moreover, higher genetically predicted proline and serine increased the risk of CAD and deep vein thrombosis (DVT), respectively. Tyrosine also showed significant causal estimates for a higher risk of angina pectoris or DVT. However, phenylalanine levels were significantly associated with a lower risk of myocardial infarction, and alanine was considered to be protective against angina pectoris (Figure 2).

Conclusion(s): This MR study demonstrated significant causal effects of circulating levels of AAs on the risk of thromboembolic diseases, revealing potential preventive strategies and therapeutic targets for CVD.