Data Sheet 1_Causal associations between abdominal obesity, dietary patterns, and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study with clinical validation.xlsx

BackgroundThe 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.
MethodsWe 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.
ResultsGenetically 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).
ConclusionOur 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.

研究背景：腹型肥胖、饮食习惯与椎间盘退变（intervertebral disc degeneration, IVDD）之间的关联尚不完全明确，从因果推断视角而言尤为如此。本研究旨在利用孟德尔随机化（Mendelian randomization, MR）分析腹型肥胖表型、饮食模式与椎间盘退变之间的潜在因果关联，并通过独立临床队列对研究结果进行验证。
研究方法：本研究利用全基因组关联研究（genome-wide association study, GWAS）汇总数据开展双向两样本孟德尔随机化分析。本研究从IEU OpenGWAS数据库中获取6种腹型肥胖表型与14种饮食模式的遗传工具变量，椎间盘退变数据则来源于FinnGen联盟（病例41669例，对照294770例）。本研究以逆方差加权（inverse-variance weighted, IVW）作为主要分析方法，辅以4种其他孟德尔随机化分析方法及敏感性分析。为验证孟德尔随机化分析结果，本研究开展了一项回顾性临床研究，纳入2020年至2024年间温州中西医结合医院的512例椎间盘退变患者与512名匹配对照。研究收集了人体测量学数据与饮食数据，并开展多变量logistic回归分析。
研究结果：遗传预测的腰围（waist circumference, WC）与腹部皮下脂肪组织（abdominal subcutaneous adipose tissue, ASAT）与椎间盘退变呈正相关（腰围：优势比（odds ratio, OR）=1.209，95%置信区间（confidence interval, CI）=1.083~1.349；腹部皮下脂肪组织：OR=1.314，95%CI=1.149~1.535）。与之相反，体质量指数（body mass index, BMI）、臀围（hip circumference, HC）及体质量指数校正后腰臀比（WHR-BMI）与椎间盘退变无显著因果关联。多种饮食模式亦与椎间盘退变存在因果关联：较高的蘑菇、粥类与白鱼肉摄入量会增加椎间盘退变风险，而苹果、谷物棒、丹麦酥皮点心、浓缩咖啡、龙虾/蟹类及其他水果的摄入则具有保护作用。临床验证进一步证实，较高的腰围（OR=1.32，95%CI=1.10~1.58）与频繁食用蘑菇（OR=1.28，95%CI=1.05~1.56）与椎间盘退变风险升高相关，而较高的水果摄入量则具有保护作用（OR=0.76，95%CI=0.62~0.93）。
研究结论：本研究结果证实，腹型肥胖——尤其是腰围与腹部皮下脂肪组织——在椎间盘退变的发生发展中发挥因果作用，且该关联独立于总体肥胖水平。此外，特定的饮食模式可显著影响椎间盘退变风险。本研究结果凸显了针对性营养干预与体成分干预在椎间盘退变预防与管理中的潜在价值，该结论同时得到了遗传学与临床证据的支持。