Causal associations between abdominal obesity, dietary patterns, and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study with clinical validation.

Background: The relationship between abdominal obesity, dietary habits, and intervertebral disc degeneration (IVDD) remains incompletely understood, particularly from a causal perspective. This study aimed to evaluate the potential causal associations between abdominal obesity traits and dietary patterns and IVDD using Mendelian randomization (MR) and to validate these findings with an independent clinical cohort. Methods: We performed a bidirectional two-sample MR analysis using genome-wide association study (GWAS) summary statistics. Genetic instruments for 6 abdominal obesity traits and 14 dietary patterns were derived from the IEU OpenGWAS database, while IVDD data were obtained from the FinnGen consortium (41,669 cases; 294,770 controls). Inverse-variance weighted (IVW) was used as the primary method, complemented by four additional MR approaches and sensitivity analyses. To validate MR results, we conducted a retrospective clinical study including 512 patients with IVDD and 512 matched controls from Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine (2020-2024). Anthropometric and dietary data were collected, and a multivariate logistic regression was performed. Results: Genetically predicted waist circumference (WC) and abdominal subcutaneous adipose tissue (ASAT) were positively associated with IVDD (WC: OR = 1.209, 95% CI: 1.083-1.349; ASAT: OR = 1.314, 95% CI: 1.149-1.535). In contrast, body mass index (BMI), hip circumference (HC), and BMI-adjusted waist-to-hip ratio (WHR-BMI) showed no significant causal relationship with IVDD. Several dietary patterns were also causally linked to IVDD: higher intake of mushrooms, porridge, and white fish increased IVDD risk, whereas apple, cereal bar, Danish pastry, espresso, lobster/crab, and other fruit intake were protective. Clinical validation further demonstrated that higher WC (OR = 1.32, 95% CI: 1.10-1.58) and frequent mushroom consumption (OR = 1.28, 95% CI: 1.05-1.56) were associated with increased IVDD risk, while higher fruit intake was protective (OR = 0.76, 95% CI: 0.62-0.93). Conclusion: Our findings support a causal role for abdominal obesity-specifically WC and ASAT-in IVDD development, independent of general adiposity. Furthermore, specific dietary patterns may significantly influence IVDD risk. These results highlight the potential of targeted nutritional and body composition interventions in the prevention and management of IVDD, currently supported by both genetic and clinical evidence.