Causal inference using genome-wide association study results of Hanwoo carcass traits: Mendelian randomization analysis

Setting breeding objectives to enhance carcass traits in Hanwoo is essential for increasing the profitability of the Hanwoo industry and ensuring that consumers receive high-quality meat. Key carcass traits, including carcass weight (CWT), eye muscle area (EMA), back-fat thickness (BFT), and marbling score (MS), are genetically correlated. Understanding the causal relationships among these traits is vital for comprehending the complex biological systems of Hanwoo. This study analyzed data from 392 Hanwoo using a Genome-Wide Association Study (GWAS) to identify genetic variants. These variants were subsequently employed as instrumental variables in a Mendelian Randomization (MR) analysis to infer causality. With CWT as the exposure variable and MS as the outcome variable, the selected instrumental variables were validated for their assumptions through tests for heterogeneity and pleiotropy. The MR analysis revealed that, except for the MR-Egger model, significant positive relationships were observed across all models, indicating that an increase in CWT causally influences an increase in MS, beyond mere genetic correlations. It was confirmed that a 1 kg increase in CWT results in an approximate 0.01-point increase in MS. Thus, this study underscores the importance of utilizing genetic variants identified through GWAS as instrumental variables for inferring causal relationships between CWT and MS via MR analysis. These findings can contribute to developing effective breeding strategies and improve our understanding of the biological mechanisms related to carcass traits.