Mining Candidate Genes and Identifying Risk Factors for Leg Disease in Broilers: A Mendelian Randomization Study

Clinical investigations have highlighted disruptions in bone metabolic processes and abnormal fluctuations in serum indicator levels during the onset of leg disease (LD) in broilers. However, the presence of a genetic causal relationship for this association remains undetermined. Therefore, the aim of this study is to discern the risk factors underlying LD development using 1235 sequenced white-feathered broilers. We employed Mendelian randomization (MR) analysis to assess the associations of bone strength (BS), bone mineral density (BMD), tibial bone weight (TBW), tibial bone length (TBL), tibial bone diameter (TBD), bone ash (BA), ash calcium (Ash Ca), ash phosphorus (Ash P), serum calcium (Ca), serum phosphorus (P), serum alkaline phosphatase (ALP), and serum osteoprotegerin (OPG) with the incidence of LD. Compelling evidence underscores a causal link between the risk of developing LD and decreased BMD (odds ratio (OR) = 0.998; 95% CI: 0.983, 0.993; P < 0.001) and narrower TBD (OR = 0.985, 95% CI: 0.975, 0.994, P = 0.002). Additionally, serum OPG concentrations (OR: 0.995, 95% CI: 0.992, 0.999, P = 0.008) were associated with BMD (OR = 0.0078, 95% CI = 0.0043 to 0.0140, P < 0.001), indicating a robust genetic relationship between ALP concentrations (OR: 0.988, 95% CI: 0.984, 0.993, P < 0.001) and TBD (OR = 0.0046, 95% CI = 0.0026, 0.0083, P < 0.001). Moreover, elevated serum Ca (OR: 0.564, 95% CI: 0.487, 0.655, P < 0.001) and P (OR: 0.614, 95% CI: 0.539, 0.699, P < 0.001) levels were associated with a narrower TBD. Elevated serum levels of Ca, P, ALP, and OPG contribute to disturbances in bone metabolism, while decreased BMD and narrower TBD are associated with a greater risk of developing LD in broilers. This discovery elucidates the metabolic risk factors for LD in broilers and could provide information on LDs, such as osteoporosis, in humans.