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Lipids and Lipid-Lowering Drugs With Risk of Intervertebral Disc Degeneration: A Mendelian Randomization Study
1Department of Spine Surgery, Ningbo No. 6 Hospital, 1059 East Zhongshan Road, Ningbo Zhejiang, 315000, China, nbdlyy.com.
Genetics Research
|July 30, 2026
Summary
Elevated high-density lipoprotein cholesterol (HDL-C) may protect against intervertebral disc degeneration (IVDD). Lipid pathways, including NPC1L1 gene expression, show potential links to IVDD, warranting further research.
Area of Science:
- Genetics
- Metabolic Disorders
- Musculoskeletal Diseases
Background:
- Intervertebral disc degeneration (IVDD) is a significant cause of low back pain.
- The role of circulating lipid traits and their associated drug targets in IVDD pathogenesis remains unclear.
Purpose of the Study:
- To investigate the causal relationship between genetically predicted lipid traits and lipid-lowering drug targets with IVDD risk.
- To explore the influence of body mass index (BMI) on these associations.
Main Methods:
- Utilized a Mendelian randomization (MR) framework with summary-level data from genome-wide association studies (GWASs).
- Analyzed associations between lipid parameters (HDL-C, LDL-C, TG) and apolipoproteins (Apoa-I, Apob) with IVDD.
- Performed multivariable MR adjusting for BMI and drug-target MR focusing on NPC1L1.
Main Results:
- Inherently elevated high-density lipoprotein cholesterol (HDL-C) was associated with reduced IVDD susceptibility.
- This protective effect of HDL-C remained significant after adjusting for BMI.
- Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-I (Apoa-I), and apolipoprotein B (Apob) showed no significant association with IVDD after correction.
- NPC1L1 gene expression was significantly associated with increased IVDD susceptibility.
Conclusions:
- Circulating HDL-C may play a protective role in intervertebral disc degeneration.
- Lipid metabolism pathways, particularly those involving NPC1L1, are implicated in IVDD.
- Further investigation into lipid pathways for IVDD prevention and treatment is warranted.
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