Shoulder impingement syndrome is a common shoulder disorder characterized by a structural narrowing of the subacromial space, which causes pain when patients raise their arms or lie on the affected side. Current research suggests that preventing obesity can reduce the incidence of shoulder joint-related diseases, and obesity is positively correlated with rotator cuff ligament injury. Moreover, body mass index (BMI) can serve as a simple method to measure the degree of obesity, as it is easy to obtain and has clear categories. However, some studies suggest that a high BMI can have a specific protective effect on the shoulder joint. Therefore, the causal relationship between BMI and shoulder impingement syndrome awaits further study.

To explore the causal relationship between BMI and shoulder impingement syndrome by combining Mendelian randomization (MR) research method with bioinformatics analysis and analysis of the global burden of disease (GBD) database.

Based on the data of genome-wide association studies (GWAS) in European populations, BMI-related single-nucleotide polymorphisms (SNP) were screened as instrumental variables. The population burden was verified, and a regression model was constructed by combining five methods, including inverse variance weighted (IVW) with gene enrichment analysis and the GBD database.

A total of 390 cases of SNP were included. The analysis by five methods, including the inverse variance weighting method, showed that: For every 1-unit increase in BMI, the risk of shoulder impingement syndrome increases by 0.2% (OR=1.002, 95% CI: 1.001-1.003). Gene enrichment analysis suggests that BMI may influence shoulder impingement syndrome through the regulation of ion channels, synaptic signal transduction, and the Rap1 signaling pathway. Drug prediction has identified potential therapeutic drugs such as lorazepam and pilocarpine acid. GBD data analysis shows that a high BMI can increase the disability-adjusted life years for musculoskeletal diseases.

The research, from both genetic causality and population burden perspectives, confirmed that high BMI is an important risk factor for shoulder impaction syndrome, providing a theoretical basis for targeted intervention. However, further verification of racial universality and molecular mechanisms is needed.