Causal effects of body mass index, education, and lifestyle behaviors on intervertebral disc disorders: Mendelian randomization study

This study aimed to investigate the causal risk factors for intervertebral disc disorders (IVDD) to help establish prevention strategies for IVDD-related diseases. We performed two-sample Mendelian randomization analyses to investigate the causal effects of body mass index (BMI), education, and lifestyle behaviors (sedentary behavior, smoking, and sleeping) on thoracic/thoracolumbar/lumbosacral IVDD (TTL-IVDD) and cervical IVDD. The inverse-variance weighted (IVW) method was conducted as the primary model to pool effect sizes using odds ratio and 95% confidence interval. The strength of causal evidence was evaluated from the effect size and different Mendelian randomization methods (MR-Egger/weighted median/weighted mode method, Cochran's Q test, leave-one-out analysis, MR Steiger, MR-PRESSO and radial IVW analyses). We found strong evidence for the causal associations between IVDD and BMI (TTL-IVDD, 1.27 [1.18, 1.37], p = 2.40 x 10(-10); cervical IVDD, 1.24 [1.12, 1.37, p = 6.58 x 10(-5)), educational attainment (TTL-IVDD, 0.57 [0.51, 0.64], p = 9.64 x 10(-21); cervical IVDD, 0.58 [0.49, 0.68], p = 1.78 x 10(-10)), leisure television watching (TTL-IVDD, 1.54 [1.29, 1.84], p = 7.80 x 10(-6); cervical IVDD, 1.65 [1.29, 2.11], p = 0.0001), smoking initiation (TTL-IVDD, 1.37 [1.25, 1.50], p = 1.78 x 10(-10); cervical IVDD, 1.32 [1.16, 1.51], p = 6.49 x 10(-5)), short sleep (TTL-IVDD, 1.28 [1.09, 1.49], p = 0.0027; cervical IVDD, 1.53 [1.21, 1.94], p = 0.0008), or frequent insomnia (TTL-IVDD, 1.20 [1.11, 1.30], p = 1.54 x 10(-5); cervical IVDD, 1.37 [1.20, 1.57], p = 7.80 x 10(-6)). This study provided genetic evidence that increased BMI, low educational attainment, sedentary behavior by leisure television watching, smoking initiation, short sleep, and frequent insomnia were causal risk factors for IVDD. More efforts should be directed toward increasing public awareness of these modifiable risk factors and mobilizing individuals to adopt healthy lifestyles.