Causal Relationships Between 4 Exposure Factors and Rotator Cuff Syndrome Using Mendelian Randomization Analysis

Although previous studies have investigated the risk factors for rotator cuff syndrome (RCS), there remains controversy due to uncontrolled and uncertain confounding factors in their analyses.

To perform Mendelian randomization (MR) analysis using single-nucleotide polymorphisms to investigate the causal relationship between RCS and 4 risk factors: type 2 diabetes mellitus (T2DM), high blood pressure (HBP), body mass index (BMI), and low high-density lipoprotein cholesterol (HDL-C).

Descriptive epidemiology study.

Genome-wide association study (GWAS) data for T2DM (ebi-a-GCST006867), BMI (ieu-b-40), HBP (finn-b-I9_HYPTENS), HDL-C (ieu-b-109), and RCS (ukb-b-50) were obtained from the IEU Open GWAS Project. The dataset of each risk factor was combined with the dataset of RCS, generating 4 datasets. Potential confounders and single-nucleotide polymorphisms related to RCS were excluded from these datasets. The causal relationships between the exposure factors and RCS were analyzed using 5 regression models: MR-Egger, weighted median estimate (WME), inverse-variance weighting (IVW), simple mode, and weighted mode. Heterogeneity in the causal effects was assessed using MR-Egger regression and IVW analyses. Sensitivity analyses were performed to determine the stability of the results.

The MR-Egger regression intercepts for T2DM, BMI, HBP, and HDL-C showed no horizontal pleiotropic effects. The results of the Cochran Q test showed P values of .075 and .080 for BMI in the MR-Egger regression and IVW models, respectively, indicating the absence of heterogeneity between BMI and RCS. The results of the weighted median estimate and IVW regression analyses showed a significant causal association between BMI and RCS, with odds ratios of 1.002 (95% CI, 1-1.004; P = .038) and 1.003 (95% CI, 1.001-1.005; P = .0003), respectively. No significant associations were found for T2DM, HDL-C, or HBP.

In the present study, BMI was positively associated with the risk of developing RCS, while T2DM, HBP, and low HDL-C were not associated with RCS development.