Causal association of education, smoking, sedentary lifestyle and body mass index with disc degeneration: Mendelian randomization

Intervertebral disc degeneration (IVDD) is a common vertebral disease, and we aimed to investigate the causal relationship between several risk factors and IVDD using Mendelian randomization (MR). We obtained summary data from public genome-wide association study databases from large sample projects. Inverse-variance weighted (IVW) was used as the primary method to estimate causal effect sizes. Several sensitivity analyses (including heterogeneity and pleiotropy tests) were performed to test the stability and reliability of the causal estimates. Univariate MR analysis showed that each 1 standard deviation increase in genetically predicted educational attainment was associated with a 43.2% reduction in the risk of IVDD (IVW; (OR) = 0.568; 95% CI [0.499-0.647]; P = 1.568 × 10-17). Smoking behavior increased the risk of IVDD by 22% (IVW; OR = 1.220; 95% CI [1.069-1.393]; P = .003), and increased hours of Watching TV and mobile phone use increased the risk of IVDD by 85.3% and 65.8%, respectively (IVW; OR = 1. 853; 95% CI [1.430-2.401]; P = 3.092 × 10-6), (IVW; OR = 1.658; 95% CI [1.222-2.251]; P = .001); and higher body mass index increased the risk of IVDD by 31.4% (IVW; OR = 1.314; 95% CI [1.213-1.424]; P = 2.382 × 10-11). Multivariate MR analysis showed that education and body mass index remained independently associated with IVDD after adjustment for other factors. Our findings support a potential causal relationship between several modifiable factors and IVDD. These findings may provide new directions for prevention and intervention strategies targeting IVDD.