Abstract

The role of obesity in the development of dorsopathies is still unclear. In this study, we assessed the associations between body mass index (BMI) and several dorsopathies including intervertebral disc degeneration (IVDD), low back pain (LBP), and sciatica by using the Mendelian randomization method. We also assessed the effect of several obesity-related traits on the same outcomes. Single-nucleotide polymorphisms associated with the exposures are extracted from summary-level datasets of previously published genome-wide association studies. Summary-level results of IVDD, LBP, and sciatica were from FinnGen. In our univariable Mendelian randomization analysis, BMI is significantly associated with increased risks of all dorsopathies including sciatica (OR = 1.33, 95% CI, 1.21–1.47, p = 5.19 × 10-9), LBP (OR = 1.28, 95% CI, 1.18–1.39, p = 6.60 × 10-9), and IVDD (OR = 1.23, 95% CI, 1.14–1.32, p = 2.48 × 10-8). Waist circumference, hip circumference, whole-body fat mass, fat-free mass, and fat percentage, but not waist–hip ratio, were causally associated with increased risks of IVDD and sciatica. Higher hip circumference, whole-body fat mass, fat-free mass, and fat percentage increased the risk of LBP. However, only whole-body fat-free mass remained to have a significant association with the risk of IVDD after adjusting for BMI with an odds ratio of 1.57 (95% CI, 1.32–1.86, p = 2.47 × 10-7). Proportions of BMI’s effect on IVDD, sciatica, and LBP mediated by leisure sedentary behavior were 41.4% (95% CI, 21.8%, 64.8%), 33.8% (95% CI, 17.5%, 53.4%), and 49.7% (95% CI, 29.4%, 73.5%), respectively. This study provides evidence that high BMI has causal associations with risks of various dorsopathies. Weight control is a good measure to prevent the development of dorsopathies, especially in the obese population.

Highlights

  • As one of the most common chronic disorders, obesity has raised alarming interest worldwide due to its significant impact on social cost and life expectancy [1]

  • Univariable Mendelian randomization (MR) was firstly performed for assessing the effects of levels of body mass index (BMI), and other obesity-related traits on intervertebral disc disease (IVDD), sciatica, and low back pain (LBP) (Supplementary Table 3)

  • Similar associations were observed for sciatica; all obesity-related traits except the waist–hip ratio increased the risk of sciatica with both the IVW method and MR-PRESSO adjustment (Figure 2)

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Summary

Introduction

As one of the most common chronic disorders, obesity has raised alarming interest worldwide due to its significant impact on social cost and life expectancy [1]. Obesity is associated with multiple musculoskeletal disorders including osteoarthritis, intervertebral disc disease (IVDD), sciatica, and low back pain (LBP) and reduced the motility and life quality of the patients [1,2,3]. Asymptomatic in various cases, disc degeneration is known to be associated with disc herniation or prolapse, low back pain, and sciatica [6,7,8]. When nerves are irritated in the lower back due to IVDD, this condition is referred to as lumbar radiculopathy. When this happens to the L4-S1 nerve roots, it leads to a commonly recognized pain called sciatica [8, 9]

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