Bidirectional Mendelian Randomization Indicates Causal Relationships Between Circulating Branched-Chain Amino Acids and Metabolic Health.

ABSTRACT: Branched-chain amino acids (BCAAs) are essential nutrients for humans. An elevated circulating BCAA level has been associated with obesity and type 2 diabetes (T2D), but the causal role of BCAAs in metabolic health remains unclear. Using a two-sample bidirectional Mendelian randomization (MR) approach, we assessed the bidirectional causal effects of circulating BCAAs on body composition, lipids, glucose metabolism, and insulin sensitivity in ∼250,000 UK Biobank participants. In MR models, a higher circulating level of BCAAs seemed to be the outcome of poor metabolic health, including higher BMI, more circulating triglycerides (TGs), lower HDL cholesterol (HDL-C), greater insulin resistance, and higher T2D risk (all P < 6 × 10-4). Conversely, a higher level of BCAAs as the exposure seemed c

SUBMITTER: Jia RY 

PROVIDER: S-EPMC12451081 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature