Genetic and Modifiable Risk Factors for Postoperative Complications of Total Joint Arthroplasty: A Genome-Wide Association and Mendelian Randomization Study.

: Total joint arthroplasty (TJA) is an orthopedic procedure commonly used to treat damaged joints. Despite the efficacy of TJA, postoperative complications, including aseptic prosthesis loosening and infections, are common. Moreover, the effects of individual genetic susceptibility and modifiable risk factors on these complications are unclear. This study analyzed these effects to enhance patient prognosis and postoperative management. : We conducted an extensive genome-wide association study (GWAS) and Mendelian randomization (MR) study using UK Biobank data. The cohort included 2964 patients with mechanical complications post-TJA, 957 with periprosthetic joint infection (PJI), and a control group of 398,708 individuals. Genetic loci associated with postoperative complications were identified by a GWAS analysis, and the causal relationships of 11 modifiable risk factors with complications were assessed using MR. : The GWAS analysis identified nine loci associated with post-TJA complications. Two loci near the and genes were significantly linked to mechanical complications and PJI, respectively. The MR analysis demonstrated that body mass index was positively associated with the risk of mechanical complications (odds ratio [OR]: 1.42; < 0.001). Higher educational attainment was associated with a decreased risk of mechanical complications (OR: 0.55; < 0.001) and PJI (OR: 0.43; = 0.001). Type 2 diabetes was suggestively associated with mechanical complications (OR, 1.18, = 0.02), and hypertension was suggestively associated with PJI (OR, 1.41, = 0.008). Other lifestyle factors, including smoking and alcohol consumption, were not causally related to postoperative complications. : The genetic loci near and influenced the risk of post-TJA mechanical complications and infections, respectively. The effects of genetic and modifiable risk factors, including body mass index and educational attainment, underscore the need to perform personalized preoperative assessments and the postoperative management of surgical patients. These results indicate that integrating genetic screening and lifestyle interventions into patient care can improve the outcomes of TJA and patient quality of life.